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Moonschi, Faruk H. "APPLICATIONS OF CELL-DERIVED VESICLES: FROM SINGLE MOLECULE STUDIES TO DRUG DELIVERY." UKnowledge, 2018. https://uknowledge.uky.edu/chemistry_etds/98.
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Single molecule studies can provide information of biological molecules which otherwise is lost in ensemble studies. A wide variety of fluorescence-based techniques are utilized for single molecule studies. While these tools have been widely applied for imaging soluble proteins, single molecule studies of transmembrane proteins are much more complicated. A primary reason for this is that, unlike membrane proteins, soluble proteins can be easily isolated from the cellular environment. One approach to isolate membrane proteins into single molecule level involves a very low label expression of the protein in cells. However, cells generate background fluorescence leading to a very low signal to noise ratio. An alternative approach involves isolating membrane proteins in artificial membrane derived vesicles. This approach is limited to proteins which can be solubilized or stabilized in detergent solution. This intermediate step endangers the structural integrity of proteins with multiple subunits. Hence, we isolated transmembrane proteins into cell-derived vesicles which maintain the proteins in their physiological membrane without compromising their functional integrity. We studied the stoichiometric assembly of α3β4 nicotinic receptors which are pentameric receptor with possible stoichiometry of (α3)2(β4)3 and (α3)3(β4)2. We found that (α3)2(β4)3 is the predominant stoichiometry, and we have verified our finding with both single and double color experiments. We have also demonstrated that cell-derived vesicles can be utilized to study ligand receptor interactions.
Cell-derived vesicles generated from cellular preparations provide a method to study the overall structural and functional properties of membrane proteins. However, organelle specific information is not available in this approach. Alternatively, separating vesicles based on their original organelle could provide information on the assembly and trafficking of membrane proteins. For example, it has been hypothesized that nicotine acts as a pharmacological chaperone of α4β2 nicotinic receptors and nicotine alters the assembly of the nicotinic receptors towards the high sensitivity isoform in the ER. To validate this hypothesis, we isolated α4β2 nicotinic receptors located on vesicles derived from the ER and plasma membrane origins and utilized single molecule studies to determine the stoichiometric assembly of the receptor. The data suggested that the ER has a higher percentage of the low sensitivity isoform ((α4)3(β2)2) than the plasma membrane indicating that the high sensitivity isoform trafficked more efficiently to the cell surface. When nicotine was added, the distribution of nicotinic receptors changes in those compartments. In both the ER and plasma membrane, the percentage of high sensitivity isoform was greater than the sample without the presence of nicotine. The results suggested that nicotine altered the assembly of nicotinic receptors to form the high sensitivity isoform in the ER and the altered assembly trafficked to the plasma membrane efficiently increasing the ratio of this isoform in the plasma membrane.
The cell derived vesicles we utilized to isolate single receptors are structurally similar to liposomes, an FDA approved drug delivery system, which is spherical vesicles composed of at least one lipid bilayer. Hence, cell-derived vesicles possess potential to be utilized as drug delivery vehicles. I explored the applicability of cell-derived vesicles as general delivery vehicles to cultured cells. Additionally, we implanted xenografts into immune compromised nude mice and prepared cell derived vesicles labeled with dye molecules. The vesicles were injected in a mouse containing a xenograft to monitor whether these vesicles can reach to the xenograft. Our data suggested that cell-derived vesicles can successfully reach the xenograft and thus have potential to be utilized as a drug delivery vehicle.
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Lofton, Megan Christina. "Development of a small molecule drug delivery vehicle for treatment of chronic pulmonary diseases." Thesis, Atlanta, Ga. : Georgia Institute of Technology, 2008. http://hdl.handle.net/1853/24706.
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Feil, Florian, Anna Sauer, Jens Michaelis, Thomas Bein, and Christoph Bräuchle. "Single molecule diffusion studies of mesoporous materials: from material science to drug-delivery applications." Diffusion fundamentals 16 (2011) 28, S. 1-2, 2011. https://ul.qucosa.de/id/qucosa%3A13761.
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Crawford, Robert. "Single-molecule DNA sensors and cages for transcription factors in vitro and in vivo." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:dc51a40b-4236-48ad-850e-e7e0010a823c.
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Gene regulation is vital to the success of all living organisms. Understanding this complex process is crucial to our knowledge of how cells function and how in some cases they can lead to debilitating or even fatal disease. In this thesis I focus on a set of DNA-binding proteins known as transcription factors (TFs), proteins fundamental to the process of gene regulation at the level of transcription. I develop assays and techniques for the detection and quantitation of TFs in vitro and in vivo as well as a method for TF encapsulation and release. The advantages of the TF detection assays in this thesis are made possible through the use of single-molecule (sm) fluorescence. This methodology enables detection of individually labeled molecules allowing discrimination of sample heterogeneities inaccessible with ensemble techniques. Here I present two different TF assays based on two sm observables: relative probe stoichiometry and Förster resonance energy transfer (FRET). The first assay design, based on stoichiometry, detects TFs using TF-dependent coincidence of two distinctly labelled DNA ‘half-sites’. I demonstrate sensitive detection (~ pM) in solution and on surfaces, multiplexed detection of multiple TFs, and detection in cell lysates. A kinetic model of the system is also developed, verified experimentally and used to quantify TF concentrations without the need for a calibration curve. The second assay design, based on FRET, is a novel approach to TF detection using TFmediated DNA bending. TFs are detected by bending the sensor and monitored with FRET at the single-molecule or ensemble level. I demonstrate TF detection in purifed form and expressed in cell lysates. As this sensor was designed for use in vivo, methods to hinder nuclease degradation are explored. For TF detection in vivo, I describe a successful strategy to internalise fluorescently labeled molecules into live E.coli. Viability and internalisation efficiency are characterised and ensemble measurements with FRET standards are demonstrated. Importantly, sm FRET measurements in vivo are achieved opening many exciting possibilities. The FRET based TF sensor is then internalised as a step towards real-time in vivo monitoring of TF concentrations. Finally a system based on DNA nanotechnology is presented for the non-covalent encapsulation and release of TFs. Such a system could be delivered into a cell to alter levels of gene expression using external stimuli as inputs. We believe these tools will generate valuable information in the study of prokaryotic gene expression as well as providing a potential commercial avenue towards diagnostics.
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Brumaru, Claudiu Stelian. "I. Hydrophobic nanoporous silica particles for biomedical applications. II. Novel approaches to two-dimensional correlation spectroscopy." Diss., University of Iowa, 2013. https://ir.uiowa.edu/etd/2446.
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Many highly effective drugs display serious side-effects. To limit them, one can contain the drug in tiny containers, which are subsequently delivered toward targets inside the body. The entrapment of drug molecules prevents them from coming in contact with and thus causing damage to normal cells. Inherently, it is difficult to reach 100% efficiency of drug trapping and release when employing physical caps to seal the vehicles. Instead, we propose drug trapping inside the nanopores of hydrophobic silica particles by "hydrophobic trapping". This phenomenon is associated with the repulsive "force field" generated inside nanometer-sized hydrophobic channels that completely prevents aqueous solutions from entering the channels. We demonstrate the excellent trapping efficiency using C18-modified silica particles with 10 nm pores and the anticancer drug doxorubicin.
The major challenge in using hydrophobic particles in biological applications is their tendency to cluster in aqueous media. To overcome it, we use surfactants as solubilization means. We have developed protocols that effectively solubilize the outer surface of the particles while preventing surfactant micelles from entering nanopores. Consequently, particles become well-dispersible in aqueous solutions, with the pre-loaded drug safely contained inside nanopores.
Nanomaterials exhibit heterogeneity on their surfaces that impact their functional applications. Although techniques such as atomic force microscopy are great tools for studying nanomaterials with their excellent spatial resolution, they cannot probe the inner surface of porous structures. We have established a method of single-molecule ratiometric imaging that is currently the only technique able to provide the nanopolarity of adsorption sites located on the pore surface. We analyze the polarity distribution of adsorptions events for the solvatochromic probe Nile Red at the C18/acetonitrile interface and discover at least two different populations of adsorption sites. One of them corresponds to the polarity of surface silanol groups while the other sites have a polarity consistent with the environment inside the C18 organic layer. We also discover an additional adsorption mode situated at a polarity higher than exposed silanol surface that could presumably be linked to a different ionization state of the silanol groups.
We are developing a method for resolving spectra of complex samples using two-dimensional hetero-correlation spectroscopy by correlating the intensity fluctuations in optical spectra to those of completely separated peaks in analytical separations. We demonstrate this methodology for fluorescence spectra and electrophoregrams of mixtures anthracene-pyrene. All the individual vibronic features that overlap in mixtures are cleanly extracted in cross-sections of the two-dimensional asynchronous spectrum.
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Wang, Xiaoyang. "Design, Construction and Investigation of Synthetic Devices for Biological Systems." University of Cincinnati / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1314041031.
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Deosarkar, Sudhir P. "Development of Novel Therapeutic and Diagnostic Approaches for Atherosclerosis." Ohio University / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1268371885.
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Dcona, Martin. "Drug Delivery Strategies Using Light Sensitive Molecules." VCU Scholars Compass, 2012. http://scholarscompass.vcu.edu/etd/445.
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Cancer remains one of the most dreaded diseases due to inevitable suffering and possible fatality. Only cardiac disease has caused more deaths than cancer. Present day cancer treatment involves radiation, surgery or chemotherapy. In chemotherapy, an anti-tumoral drug is used to treat the tumor either by killing or stalling the growth of the tumor cells. In certain types of cancer, for e.g. metastatic breast cancer, the first line of therapy is often chemotherapy. But the inability of current clinically approved drugs to selectively target tumor cells, ultimately results in side effects. To reduce these side effects, prodrug therapies have been developed. A prodrug is defined as a drug molecule inactivated by a temporary cap or carrier, subsequently removed by an external intra or extracellular stimulus. Several prodrug strategies such as ADEPT (Antibody–Directed Enzyme Prodrug Therapy) have been tested in clinical trials but have thus far met with limited success. In the wake of these limitations, development of photo-activatable prodrugs may be particularly desirable for minimizing the adverse side effects associated with current cancer chemotherapeutics. Photodynamic therapy (PDT) is a light dependent tumor treatment modality that has existed for many years. PDT involves a photosensitizer which is administered to the patient and later activated using the light of wavelengths between 650-800 nm. The activated photosensitizer creates singlet oxygen, which acts as cytotoxic agent to the tumor cells. But this approach has several drawbacks including slow uptake of the photosensitizer by the tumor cells and the dependence on molecular oxygen that is not always present at even moderate levels in the tumor tissues. To address these limitations of PDT, we developed a new prodrug concept called ‘Photocaged Permeability’ in our first project, and demonstrated drug delivery using this approach. The basis of this concept is that, by attaching a hydrophilic molecule to the drug via a photosensitive linker, the permeability of the drug could be restrained. But the drug could be released at the site of the tumor after irradiating with UV light. To achieve this goal, we designed and synthesized a photosensitive drug conjugate that was comprised of doxorubicin attached to a negatively charged, cell impermeable molecule, EDANS (5-((2-Aminoethyl) amino) naphthalein-1-sulfonic acid) via a photosensitive nitroveratryl linker. Later, we performed MTT (cell viability) assays using esophageal adenocarcinoma (JH-EsoAd1) cells to determine the efficiency of our drug conjugate to induce cell death. As expected our drug conjugate was able to induce cell death, but only in presence of light. But in the dark, the cells remained unaffected. Also, we did several control studies to substantiate the fact that the cell death was actually due to drug release but not due to light or other entities. Further, we performed FACS (Fluorescence Assisted Cell Sorting) and confocal assays to show that in dark, the drug conjugate did not permeate cells. But upon irradiation with UV light, the drug was released from the conjugate, permeated the cells and induced cell death. A weakness of the above mentioned approach is that the drug is “decaged” or photo-released from the conjugates only under UV light; which cannot be translated to physiological conditions. This is because the UV light cannot penetrate deeper than 5 mm into the human skin. As a result, tumor cells that are deeply embedded in the human body cannot be treated using these approaches. To address this problem, Near Infrared (NIR) light could be used as it penetrates deeper than UV. Recently, several groups have reported using Upconverting Nanoparticles (UCNP) for the purpose of drug activation. The basis of this phenomenon is that the incidence of NIR light on these particles initiates multi-photon processes, eventually emitting UV/VIS wavelengths. The advantage of the NIR is that it deeply penetrates into the human skin. In our latest project, we have designed a drug conjugate that would be attached to UCNPs. We envision that after grafting the drug conjugate onto the nanoparticles and irradiating it with NIR drug release will occur as a result of upconversion. The above two systems describes novel methodologies for controlled release of the drug. To further improve the efficacy of the drug action, we designed new photosensitive systems based on the concept of targeted drug delivery. Targeted drug delivery is a treatment methodology in which the modified chemotherapeutic drug with higher tumor affinity could be concentrated in the tumor tissues. In certain cases, the receptors of tumor cells are targeted for the purpose of therapy. Receptors are cell surface proteins that are expressed on their plasma membrane. A select few of them such as Folic Acid Receptor (FAR) and PSMA (Prostate Specific Membrane Antigen) are overexpressed in malignant cells. In our new designs, we attached folic acid and urea based (DUPA) ligand, which were previously reported to bind to FAR and PSMA receptors respectively. Cell studies are currently underway to determine the specificity of these drug conjugates in targeting tumor cells. Once we demonstrate the above drug delivery strategies in vitro and later in vivo, we will have established novel drug delivery systems that could potentially be applied towards chemotherapeutic treatment.
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Pan, Xiaogang. "Design and evaluation of lipid based delivery systems for delivery of small molecules and macro-molecular nucleotides based therapeutic agents." Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1164679618.
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Cleroux, Carolyne. "Biodegradable nanoparticles for sustained occular drug delivery." Thesis, University of Ottawa (Canada), 2010. http://hdl.handle.net/10393/28485.
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Apoptosis (programmed cell-death) is a common final pathway through which cells die in retinal degenerative diseases. The purpose of this project was to develop biodegradable nanoparticles that quickly deliver XIAP, an inhibitor of apoptosis, to retinal cells following acute insults. In vitro protein release profiles from different formulations were established, and two cell types were incubated with nanoparticles to assess cellular uptake. Subretinal injections were carried out in rats to assess in vivo localization and possible toxicity. In vitro studies showed an initial burst of protein followed by sustained release, with overall low levels of protein release. Cell culture experiments suggest that particles are mostly membrane-bound, and some may be internalized. In vivo experiments revealed no signs of toxicity, and protein localized within the photoreceptor layer. In conclusion, nanoparticles may provide a good delivery system for XIAP; however higher levels of protein release are needed for neuroprotection, warranting further investigation.
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Twyman, Lance James. "The synthesis and applications of dentrimeric molecules." Thesis, University of Kent, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.259718.
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Pavurala, Naresh. "Oral Drug Delivery -- Molecular Design and Transport Modeling." Diss., Virginia Tech, 2013. http://hdl.handle.net/10919/53505.
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One of the major challenges faced by the pharmaceutical industry is to accelerate the product innovation process and reduce the time-to-market for new drug developments. This involves billions of dollars of investment due to the large amount of experimentation and validation processes involved. A computational modeling approach, which could explore the design space rapidly, reduce uncertainty and make better, faster and safer decisions, fits into the overall goal and complements the product development process. Our research focuses on the early preclinical stage of the drug development process involving lead selection, optimization and candidate identification steps. Our work helps in screening the most favorable candidates based on the biopharmaceutical and pharmacokinetic properties. This helps in precipitating early development failures in the early drug discovery and candidate selection processes and reduces the rate of late-stage failures, which is more expensive.
In our research, we successfully integrated two well-known models, namely the drug release model (dissolution model) with a drug transport model (compartmental absorption and transit (CAT) model) to predict the release, distribution, absorption and elimination of an oral drug through the gastrointestinal (GI) tract of the human body. In the CAT model, the GI tract is envisioned as a series of compartments, where each compartment is assumed to be a continuous stirred tank reactor (CSTR). We coupled the drug release model in the form of partial differential equations (PDE's) with the CAT model in the form of ordinary differential equations (ODE's). The developed model can also be used to design the drug tablet for target pharmacokinetic characteristics. The advantage of the suggested approach is that it includes the mechanism of drug release and also the properties of the polymer carrier into the model. The model is flexible and can be adapted based on the requirements of the clients. Through this model, we were also able to avoid depending on commercially available software which are very expensive.
In the drug discovery and development process, the tablet formulation (oral drug delivery) is an important step. The tablet consists of active pharmaceutical ingredient (API), excipients and polymer. A controlled release of drug from this tablet usually involves swelling of the polymer, forming a gel layer and diffusion of drug through the gel layer into the body. The polymer is mainly responsible for controlling the release rate (of the drug from the tablet), which would lead to a desired therapeutic effect on the body.
In our research, we also developed a molecular design strategy for generating molecular structures of polymer candidates with desired properties. Structure-property relationships and group contributions are used to estimate the polymer properties based on the polymer molecular structure, along with a computer aided technique to generate molecular structures of polymers having desired properties. In greater detail, we utilized group contribution models to estimate several desired polymer properties such as grass transition temperature (Tg), density (ρ) and linear expansion coefficient (α). We subsequently solved an optimization model, which generated molecular structures of polymers with desired property values. Some examples of new polymer repeat units are - [CONHCH₂ - CH₂NHCO]n -, - [CHOH - COO]n -. These repeat-units could potentially lead to novel polymers with interesting characteristics; a polymer chemist could further investigate these. We recognize the need to develop group contribution models for other polymer properties such as porosity of the polymer and diffusion coefficients of water and drug in the polymer, which are not currently available in literature.
The geometric characteristics and the make-up of the drug tablet have a large impact on the drug release profile in the GI tract. We are exploring the concept of tablet customization, namely designing the dosage form of the tablet based on a desired release profile. We proposed tablet configurations which could lead to desired release profiles such as constant or zero-order release, Gaussian release and pulsatile release. We expect our work to aid in the product innovation process.Ph. D.
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Mitra, Deboleena. "Light Mediated Drug Delivery Using Photocaged Molecules and Photoswitchable Peptides." VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/3618.
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There are many different types of targeted therapy for cancer treatment. The method of light mediated targeted therapy that we have developed uses photocaged molecules and photoswitchable peptides.
In photocaging, a biologically active molecule is made inactive by the attachment of a photocleavable blocking group. On exposure to UV radiation the photocleavable entity is removed and the biologically active molecule is released. Using this concept we have designed a prodrug that consists of a cell impermeable hydrophilic molecule attached to a photocaged doxorubicin. Upon irradiation with UV light the photosensitive group is removed and cytotoxic doxorubicin is released at the tumor site. This concept has been further modified by attaching receptor binding molecules to the photocaged entity to increase its specificity.
A peptide which consists of an azobenzene photoswitch has been used which, in the dark state is randomly coiled and cell impermeable but upon illumination becomes helical and cell permeable and can be used to deliver drugs into the cells. Upon illumination with UV light of suitable wavelength the azobenzene linker will change from a trans to a cis form and this will convert the randomly coiled cell impermeable peptide into an α helical permeable form. Thus a series of peptides have been designed with different arginine mutations which develop an arginine patch in the helical form. This arginine patch would help in cell permeability by interacting with cell surface glycans. The method could potentially be used to deliver drugs into cells in presence of light.
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Wahab, Habibah Bin. "Effect of a penetration enhancer on lipid membranes : a molecular dynamics study." Thesis, King's College London (University of London), 1999. https://kclpure.kcl.ac.uk/portal/en/theses/effect-of-a-penetration-enhancer-on-lipid-membranes--a-molecular-dynamics-study(15d6388d-136f-4763-90d1-71ff975b6869).html.
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Comenge, Farre Joan. "Gold Nanoparticles as Drug Delivery Agents. Detoxifying the Chemotherapeutic Drug Cisplatin." Doctoral thesis, Universitat Autònoma de Barcelona, 2013. http://hdl.handle.net/10803/125963.
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L’ús de nanopartícules (NPs) ha emergit com una eina prometedora pel tractament de càncer. Entre els seus usos en teràpia i en tècniques d’imatge, destaca l’ús com agents de direccionament de fàrmacs. Tot i així, encara es requereix un profund coneixement d’aquests sistemes abans de poder aplicar-los a la clínica. Aquí presentem l’ús de nanopartícules d’or (AuNPs) per a detoxificar un dels fàrmacs de major ús en quimioteràpia, el cisplatí. Aquest fàrmac està lligat a la NP via un enllaç de coordinació sensible a pH per assegurar l’alliberament de fàrmac als endosomes.
El tamany de les NPs juga un paper molt important en determinar algunes respostes biològiques com la biodistribució o la seva remoció per part del sistema immune. Per això, és indispensable controlar perfectament el tamany de la NP en la seva síntesis abans de qualsevol aplicació biològica. Aquí descrivim un nou protocol per sintetitzar AuNPs amb un control exquisit del tamany entre 5 i 200 nm. Un dels avantatges d’aquest protocol és l’obtenció de NPs estabilitzades amb citrat que poden ser funcionalitzades a posteriori. D’aquesta manera podem aprofundir aquí en el mecanisme de formació de monocapes autoensamblades (SAM) i capes formades per barreges de surfactants. El control pel que fa a la composició i conformació d’aquestes és molt important doncs determina respostes biològiques com l’adsorció de proteïnes i l’estabilitat col·loïdal en medis fisiològics. Aquests conjugats han servit com a esquelet per enllaçar-hi cisplatí via la formació d’un enllaç de coordinació que asseguri un alliberament de la droga desencadenat per una baixada de pH. Aquesta conjugació està caracteritzada en profunditat per tal de garantir la estabilitat col·loïdal així com la de l’enllaç.
Finalment, el disseny del conjugat té efectes significatius en les propietats farmacocinètiques, en l’evolució del propi conjugat i en la manca de toxicitat. En aquest treball mostrem en models animals com la toxicitat deguda a cisplatí disminueix clarament sense afectar això a les propietats terapèutiques del fàrmac. A més a més, les NPs no només actuen com a vehicles sinó que també protegeixen el fàrmac contra la inactivació per part de proteïnes del sèrum fins que els conjugats són internalitzats per cèl·lules i el cisplatí alliberat. La possibilitat de seguir el fàrmac (Pt) i el vehicle (Au) separadament en funció de l’òrgan i el temps aporta també un millor coneixement sobre com els nanovehicles són processats per l’organisme.The use of nanoparticles (NPs) has emerged as a potential tool to improve cancer treatment. Among the proposed uses in imaging and therapy, their use as a drug delivery scaffold has been extensively highlighted. However, there are still some controversial points which need a deeper understanding before applying them in the clinics. Here, it is presented the use of gold nanoparticles (AuNPs) to detoxify the antitumoral agent cisplatin linked to the nanoparticle via a pH sensitive coordination bond for endosomal release. Since size of NPs plays an important role in determining biological responses such as biodistribution or clearance by immune system, a perfect control on the synthesis of AuNPs is required previously to any biological application of these AuNPs. It is described in this work a new synthetic protocol of biocompatible AuNPs with a perfect control of the size between 5 to 200 nm. One of the advantages of this protocol is the obtaining of citrate-capped AuNPs that can be further functionalized. This allowed us to provide insights on the mechanism of Self-Assembled Monolayers and mixed layers formation. The control of the mixed layer composition and conformation is important since it determines biological outcomes such as protein adsorption and colloidal stability in physiological media. These AuNPs conjugates are used as scaffold for cisplatin attachment via the formation of a coordination bond that ensures a pH-triggered release of the drug. This conjugation is deeply characterized to ensure the maintenance of colloidal and link stability on working conditions. Finally, the NP conjugate design has important effects on pharmacokinetics, conjugate evolution and biodistribution and absence of observed toxicity. Here we show that cisplatin-induced toxicity is clearly reduced without affecting the therapeutic benefits in mice models. The NPs not only act as carriers, but also protect the drug from deactivation by plasma proteins until conjugates are internalised in cells and cisplatin released. Also, the possibility to track the drug (Pt) and the vehicle (Au) separately as a function of organ and time enables a better understanding of how nanocarriers are processed by the organism.
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Zhang, Mengzi. "DEVELOPMENTS OF LIPID-BASED NANOPARTICLES FOR THERAPEUTIC DRUG DELIVERY." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1417025932.
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Weight, Alisha K. (Alisha Kessel). "Enhancing pharmaceutical formulations to improve efficacy and delivery of drug molecules." Thesis, Massachusetts Institute of Technology, 2013. http://hdl.handle.net/1721.1/82323.
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Thesis (Ph. D. in Biological Chemistry)--Massachusetts Institute of Technology, Dept. of Chemistry, 2013.Cataloged from PDF version of thesis.
Includes bibliographical references.
Major impediments to the full utility of current and potential drugs include issues of resistance and delivery. To address these challenges, in this thesis two directions of research were pursued: (1) the use of multivalent polymeric inhibitors to overcome drug resistance in human and avian influenza and (2) low-viscosity, high-concentration protein suspensions for therapeutic antibody, in particular monoclonal antibody (MAb), delivery. (1) Influenza resistance to small molecule neuraminidase (NA) inhibitors is spreading. Little emphasis, however, has been placed on alternative formulations of inhibitors. We investigated the design of multivalent antivirals, wherein small molecule ligands of viral proteins are conjugated via a linker to a linear polymeric backbone. Unexpectedly, we found that a poly-L-glutamine bearing pendant zanamivir (ZA) groups is at least as potent as those containing both ZA and sialic acid (SA). By examining the structure-activity relationship of such monofunctional conjugates, we show that the most potent one has 10% ZA attached to a neutral, high molecular weight backbone through a short alkyl linker. Importantly, we also demonstrate that such a polymer conjugate entirely compensates for weakened binding in and has 2,000-fold enhanced anti-viral potency against, ZA-resistant strains. We further evaluated this optimized inhibitor in vivo and observed that it is an effective therapeutic of established infection in ferrets and reduces viral titers up to 190-fold when used as a combined prophylactic/therapeutic in mice. Additionally, we see no evidence that the conjugate stimulates an immune response in mice upon repeat administration. (2) Typically, high doses of MAb therapeutics are required for clinical effect. Ideally, these MAbs would be delivered by subcutaneous injection of a small liquid volume. Such highly concentrated MAb solutions, however, are far more viscous than the 50 centipose (cP) permitted by the FDA. We evaluated approaches to reduce formulation viscosity by forming protein suspensions. Aqueous suspensions induced by poly(ethylene glycol), precipitating salts, or ethanol actually increased viscosity. However, non-aqueous suspensions of amorphous antibody powders in organic solvents that have s 1 hydrogen atom available for hydrogen-bonding, exhibited up to a 38-fold decrease in viscosity.
by Alisha K. Weight.
Ph.D.in Biological Chemistry
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Skilling, Kathryn J. "Low molecular mass nucleoside gelators for intra-tumoural drug delivery." Thesis, University of Nottingham, 2016. http://eprints.nottingham.ac.uk/33222/.
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There are numerous chemotherapeutic agents available today that treat a wide array of tumours. The majority of these compounds are administered via intravenous (i.v.) infusion in large doses (1000 mg/m2), necessary to sustain a desired therapeutic effect. The systemic nature of the drug delivery, the dosage size and non-specific nature of many chemotherapeutic agents however means that they attack any rapidly dividing tissue system, leading to the commonly observed side effects e.g. alopecia, nausea, neutropenia and thrombocytopenia. Low molecular weight gelators (LMWGs) are increasing in popularity as an alternative platform for drug delivery. They are typically small amphiphilic organic molecules which self-assemble in water forming a 3D gel network; they offer advantages over other drug delivery platforms as they are typically derived from biological polymers and are therefore inherently biocompatible. Using the nucleoside gemcitabine; a first-line treatment for the treatment of gastric and pancreatic cancer as a model drug, two localised delivery systems were developed. The first, an inert LMWG matrix for the encapsulation and passive release of gemcitabine and the second, a therapeutic molecular gel derived from the chemotherapeutic itself. Cytidine, an inert analogue of gemcitabine was used to develop a passive delivery system. Regioselective synthesis of N-acylated derivatives of varying chain lengths was achieved via an activated triazine ester. Using a minimal amount of ethanol and an ‘anti-solvent’ switch gelation method a gelating system derived from the N-myristoyl derivative, containing a solvent volume fraction (ΦSOL) of 0.40 was found to have the most advantageous mechanical and structural properties; a crosslinked nanofibrillar network, established by rheological measurements and microscopy (TEM). The gel was validated as a drug delivery platform via encapsulation and release low molecular weight fluorescein and high molecular weight FITC Dextran, with the gelator matrix releasing the smaller fluorescein and retarding the release of the higher molecular weight dextran. Further modification and optimisation of the passive system afforded an N-octanoyl 2’-deoxycytidine conjugate that underwent molecular reorganisation into a cross-linked nanofibrillar structure in a 100 % aqueous environment. This gel was the first of its kind to assemble in this manner and the rheological measurements demonstrate its self-healing properties, whilst encapsulation of fluorescents once again demonstrated controlled release of low molecular weight fluorescein over a 24 h period. In vitro growth inhibition assays validated the platform as biologically compatible against gastric (MKN-7) and pancreatic (MIA PaCa-2) cell lines. Additional modification of the chemotherapeutic itself laid the foundation for an intra-tumoural targeted therapeutic delivery system. Enzyme cleavable pro-drugs of gemcitabine were created with amphiphilic properties, linkages designed to undergo varying rates of hydrolysis from both the N-amino and 5ʹ-hydroxyl positions. Whilst no successful gelating entities were achieved, the N-amide and 5’-ester prodrugs were found to have comparable potencies to the parent compound in vitro when tested against gastric and pancreatic cell lines. From the results obtained during this work, it can be concluded that with further chemical modification based upon parameters discussed here on in that a LMWG system could be a viable platform for drug delivery in the future.
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Ray, Judith Victoria. "Novel molecular imprinted nanogels as drug delivery vehicles for tamoxifen." Thesis, Queen Mary, University of London, 2014. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8856.
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The field of nanomedicine has witnessed an incredible expansion, from a total market value in 2003 of $500 million expected to rise to $160 billion by 2015 (Global Industry Analysts, Inc.). The nanomedicine industry is forecasted to grow and have a significant impact on the economy, with sectors such as biomaterials, diagnostics and drug delivery expected to play a major role. This thesis gives a detailed account of the synthesis and characterisation of molecularly imprinted nanogels for drug delivery. Their toxicity and potential use as a targeted carrier to cancerous cells is evaluated. Initially an overview of nanomaterials and their uses in many areas such as agriculture, energy storage and technology are discussed. The impact of nanomaterials on the life sciences is examined; in particular their application in drug delivery is focussed upon. Chapters 2, 3 and 4 make up the results and discussion of this work. Chapter 2 focuses on developing the synthesis of the acrylamide based nanogels and, vitally, incorporating a suitable fluorescent tag in order to track the nanogels in vitro and in vivo. Fundamentally toxicity studies carried out on the nanogels, both in vitro and in vivo in Danio rerio (zebrafish) are reported in Chapter 3 to ensure the nanogels are biocompatible. Chapter 4 introduces an innovative approach, molecular imprinting, to incorporating a drug into the nanogels. The upload and release of Tamoxifen (a drug used to treat breast cancer) at reduced pH, was also analysed. Finally future development of the carrier is discussed and key issues that need to be addressed.
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Wong, Ling Wai. "Molecular delivery system based on the nanoporous zeolite microstructures /." View abstract or full-text, 2006. http://library.ust.hk/cgi/db/thesis.pl?BIEN%202006%20WONG.
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Teng, Yue. "Solubilization and release studies of small molecules in polymeric micelles /." Digital version accessible at:, 2000. http://wwwlib.umi.com/cr/utexas/main.
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Sakhalkar, Harshad S. "Enhanced Adhension of Biodegradable Drug Delivery Vehicles to Inflamed Endothelium." Ohio University / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1129916752.
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Wood, Kris Cameron. "Nanostructured gene and drug delivery systems based on molecular self-assembly." Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/39350.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2007.Includes bibliographical references.
Molecular self-assembly describes the assembly of molecular components into complex, supramolecular structures governed by weak, non-covalent interactions. In recent years, molecular self-assembly has been used extensively as a means of creating materials and devices with well-controlled, nanometer-scale architectural features. In this thesis, molecular self-assembly is used as a tool for the fabrication of both gene and drug delivery systems which, by virtue of their well-controlled architectural features, possess advantageous properties relative to traditional materials used in these applications. The first part of this thesis describes the solution-phase self-assembly of a new family of linear-dendritic "hybrid" polymers with plasmid DNA for applications in gene therapy. It begins with an overview of the design of next-generation, non-viral gene delivery systems and continues through the synthesis and validation of hybrid polymer systems, which possess modular functionalities for DNA binding, endosomal escape, steric stabilization, and tissue targeting. This part of the thesis concludes with applications of these systems to two areas of clinical interest: DNA vaccination and tumor targeted gene therapy.
(cont.) The second part of this thesis describes the directed self-assembly of polymeric thin films which are capable of degrading in response to either passive or active stimuli to release their contents. It begins with a description of passive release thin films which degrade by basic hydrolysis to release precise quantities of model drug compounds. These systems can be engineered to release their contents on time scales ranging from hours to weeks and can also be designed to release multiple drugs either in series or in parallel. Later, field-activated thin films which release their contents in response to an external, electrical stimulus are described and characterized in detail. Together, these approaches combine rapid and inexpensive processing, the ability to conformally coat any surface regardless of composition, size, or shape, and the ability to release multi-drug or multi-dose schedules, and as such they may find applications in a range of areas.
by Kris Cameron Wood.
Ph.D.
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Angelos, Sarah Ann. "Molecular machines supported on mesoporous silica nanoparticles for drug delivery applications." Diss., Restricted to subscribing institutions, 2009. http://proquest.umi.com/pqdweb?did=1835827851&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
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Hashmi, Sumaiya F. "A DNA Computer for Glioblastoma Multiforme Diagnosis and Drug Delivery." Scholarship @ Claremont, 2013. http://scholarship.claremont.edu/cmc_theses/799.
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Glioblastoma multiforme (GBM) is a debilitating malignant brain tumor with expected patient survival of less than a year and limited responsiveness to most treatments, often requiring biopsy for diagnosis and invasive surgery for treatment. We propose a DNA computer system, consisting of input, computation, and output components, for diagnosis and treatment. The input component will detect the presence of three GBM biomarkers: vascular endothelial growth factor (VEGF), caveolin-1α (CAV), and B2 receptors. The computation component will include indicator segments for each of these genes, and ensure that output is only released if all the biomarkers are present. The output component will consist of the therapeutic agent interleukin-12 (IL-12).
This study will designate four groups of animals: untreated tumor-free (control), tumor-inoculated (RG2), treated and tumor-free (DNA), and treated and tumor-inoculated (RG2/DNA). In the RG2 and RG2/DNA groups, we will inoculate adult male Fischer rats with RG2 cells into the striatum to induce tumor growth. Rats in the DNA and RG2/DNA groups will be implanted with the DNA system at the same location via recombinant adeno- associated viral vectors. The effectiveness of the DNA system will be evaluated through tumor size measurements, collected from brain slices stained with hematoxylin and eosin, and survival curve. Additionally, IL-12 localization will confirm the release of the output component.
We anticipate that the DNA treatment will result in a decrease in tumor size, leading to smaller tumor size in the RG2/DNA group versus the RG2 group. The control group is expected to survive the longest, followed by the DNA group, then the RG2/DNA group, and finally the RG2 group. In the DNA group, IL-12 is expected to stay localized to the implantation site, remaining in its unreleased stem-loop form. On the other hand, it is expected to be released and active in the RG2/DNA group.
This study provides a proof of concept to demonstrate the viability and effectiveness of a DNA system using VEGF, CAV, and B2 receptors as biomarkers and IL-12 as a therapeutic output component in the RG2 model. Further research may include varying several of the parameters used in this study, including amount of RG2 administered, choice of biomarkers, quantity and choice of output component, and choice of animal model. This system provides a promising and innovative new approach that is less invasive than surgery yet is still effective in diagnosing, targeting, and treating GBM.
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Armishaw, Olga Anne. "Molecular studies of organometallic carbohydrates and related compounds." Thesis, Robert Gordon University, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.360997.
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Saito, Takashi. "DESIGN AND CHARACTERIZATION OF GELATIN HYDROGELS INCORPORATING LOW-MOLECULAR-WEIGHT DRUGS FOR TISSUE REGENERATION." 京都大学 (Kyoto University), 2015. http://hdl.handle.net/2433/199334.
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Ali, Maryam Byrne Mark E. "Therapeutic contact lenses for comfort molecules." Auburn, Ala., 2007. http://hdl.handle.net/10415/1334.
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Gerayeli, Faezeh. "Stimulated delivery of therapeutic molecules from hydrogels using ultrasound." Thesis, Université Grenoble Alpes (ComUE), 2017. http://www.theses.fr/2017GREAS019/document.
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Le doctorant n'a pas fourni de résumé en françaisThe research described in this thesis is directed to study an externally stimulated DDS that incorporates a hydrogel as the matrix for the therapeutic agent. The research does not investigate a particular site for the delivery of the therapeutic agent. However, the aim of this research program is to develop various hydrogel formulations with desirable characteristics and structures from which the drug release can be controlled with applied external energy in the form of low-frequency ultrasound. To accomplish this, two types of natural hydrogels from agarose and chitosan and one type of synthetic hydrogel from PVA were fabricated. Parameters that affect the structure were varied for each type of hydrogel in order to study the effect of structural changes on drug loading and release capacity of hydrogels. Next, the obtained hydrogels were assessed for the delivery of Theophylline as the model drug.Among the three types of hydrogels, chitosan was found to have the fastest swelling rates and the higher water uptakes while the least swelling was found with PVA hydrogels and then agarose hydrogels crosslinked at pH 12. Regarding the mechanical stability of hydrogels, the ranking of the elastic modulus was PVA hydrogels (highest), then agarose hydrogels and chitosan copolymers (lowest). It seemed that the more mechanically stable structure of the PVA hydrogels correlated with a reduced mobility of water, in comparison to the greater mobility of water in the mechanically weaker chitosan copolymers.The stimulated and passive release of Theophylline from those hydrogel carriers showed how ultrasound, as an external energy, stimulates and controls the release of the drug. The measurements confirmed that it is only the energy imparted by the longitudinal ultrasonic waves that act on the polymeric network. The mechanism by which the ultrasound affects the release is considered as a form of a ratchet motor. The polymer chains play the role of the “ratchet” steps and the ultrasonic waves accelerate the particle movement in the release media. Hence, once the ultrasound is applied, the particles descend chain-to-chain (i.e. step-by-step) driven down their concentration gradient by the applied energy until they reach the surface of the hydrogel and hence are released into the surrounding media.Increasing the ultrasound intensity vastly accelerates the drug release. Indeed a higher intensity equals a higher energy transferred from the ultrasonic waves to the drug particles, resulting in faster and less controlled release. This also depends on the type of drug carrier structure. If the hydrogel carrier is mechanically stable, such as the PVA samples or the agarose hydrogels crosslinked at pH 12, the effect of high ultrasound intensity is much less compared to a less mechanically stable carrier such as the chitosan blends. Ultrasound applied for a longer period of time increases the amount of drug released, with the consequent effect of increasing the amount of heat generated in the hydrogel. Generally, a longer duration of the applied energy results in a greater amount of energy absorption, and an increase in friction and heat generation. These effects are important considerations in relation to the heat sensitivity of the drug to be delivered and the thermal characteristics of the polymeric carrier.This PhD research has demonstrated that both natural and synthetic hydrogels coupled to an ultrasonic energy source provides a controllable DDS, which provide some novel outcomes and contributions to the body of knowledge in the field of controlled drug delivery
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Zhang, Ning. "Design of high molecular weight polymerized hemoglobins for use in transfusion medicine and monocyte/macrophage hemoglobin-based drug delivery systems." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1318952866.
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Sodha, Anirudhasingh. "DEVELOPMENT AND COMMERCIALIZATION OF HEPATOCYTE TARGETED DRUG DELIVERY VEHICLE FOR PHARMACEUTICAL APPLICATION." Case Western Reserve University School of Graduate Studies / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1247192896.
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Leves, Natalia. "Nanopartículas de grafite para carreamento de antiinflamatórios não esteroidais por estudos de docking molecular." Universidade Federal de São Carlos, 2013. https://repositorio.ufscar.br/handle/ufscar/7035.
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Previous issue date: 2013-08-13The non steroidal anti-inflammatory drugs have been known for over 100 years and has been widely used by mankind. However cause adverse effects, since gastrointestinal complications to cardiac diseases many of these symptoms related to its nonspecific action in biological systems. Thus, the proposal of a drug delivery system for loading these drugs to the site of inflammation, could reduce these unwanted effects in the body due to the limitation of more targeted effects beyond its site of action.In this study, the graphene and graphite plates were used as carriers, since studies demonstrate the usefulness of other conformational structures of carbon as drug carriers for the treatment of cancer, for example. Two models were studied for the plates by softwares of molecular docking: template sandwich, which comprises two carbon plates, with ligant between them, and the model surfing with one carbon plate comprising the ligant. The compounds were obtained from data banks, such as CSD, PDB and SD, the plates were obtained by molecular modeling. The analysis of intermolecular interactions, essential knowledge for understanding the structures obtained was done using molecular imaging with high resolution. The experimental results showed that the in silico model sandwich was the most favorable for this system, providing stability and protection for the ligand that this does not become detached from the plates during the path taken in the body to the desired location.
Os anti-inflamatórios não esteroidais são conhecidos há mais de 100 anos e vem sendo amplamente utilizados pela humanidade. No entanto, causam efeitos adversos, desde problemas gastrointestinais até complicações cardíacas, muitos desses sintomas relacionados com sua ação inespecífica nos sistemas biológicos. Dessa forma, a proposta de um sistema de drug delivery para o carreamento desses fármacos até o local da inflamação, poderia reduzir esses efeitos indesejados no organismo devido a limitação de alvos mais específicos além do seu local de ação. No presente estudo, foram utilizadas placas de grafeno e grafite como carreadores, uma vez que estudos demonstram a utilidade de outras estruturas conformacionais do carbono como carreadores de fármaco para o tratamento de câncer, por exemplo. Foram estudados dois modelos para as placas por meio de software de docking molecular: modelo sandwich, o qual engloba duas placas de carbono, com os ligantes entre elas, e o modelo surf, com uma placa de carbono comportando o ligante. Os compostos estudados foram obtidos dos bancos de dados como CSD, SD e PDB e as placas foram obtidas por modelagem molecular. A análise das interações intermoleculares, conhecimento essencial para o entendimento das estruturas obtidas, foi feita utilizando visualização molecular de alta resolução. Os resultados dos experimentos in silico mostraram que o modelo sandwich foi o mais favorável para esse sistema, posto que confere estabilidade e proteção ao ligante para que este não se desprenda das placas durante o caminho percorrido pelo organismo até o local desejado.
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De, la Torre Paredes Cristina. "Nanotechnology and supramolecular chemistry in controlled release and molecular recognition proceses for biomedical applications"." Doctoral thesis, Universitat Politècnica de València, 2018. http://hdl.handle.net/10251/94043.
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La presente tesis doctoral, titulada "Nanotecnología y química supramolecular en procesos de liberación controlada y reconocimiento molecular para aplicaciones biomédicas", se centra en dos temas importantes: el reconocimiento molecular y los procesos de liberación controlada.
Esta tesis doctoral está estructurada en cuatro capítulos.
El primer capítulo introduce el concepto de materiales híbridos orgánicos-inorgánicos funcionalizados con puertas moleculares y sus aplicaciones biomédicas como nanomateriales para dirigir y controlar la liberación controlada de fármacos. Además se introduce una breve descripción sobre sensors colorimétricos basados en la base de la quimica supramolecular, particularmente en los procesos de reconocimiento molecular.
En particular, el capítulo 2 describe la preparacion de cinco nanodispositivos que responden a enzimas. Estos materiales híbridos se componen de dos unidades principales: un soporte mesoporoso basado en sílice inorgánica, capaz de encapsular moléculas orgánicas y un compuesto orgánico anclado en la superficie externa del soporte mesoporoso inorgánico que actúa como puerta molecular. Todos los sistemas propuestos utilizan puertas moleculares peptídicas que responden a temperatura o enzimas como estímulo.
La segunda parte de esta tesis doctoral se centra en el diseño y desarrollo de un nuevo compuesto químico capaz de detectar monóxido de carbono in vivo.
En resumen, para todos los resultados antes mencionados podemos decir que esta tesis doctoral constituye una contribución científica original al desarrollo de la química supramolecular. Sus resultados derivados de los estudios presentados dejan rutas abiertas para continuar el estudio y el desarrollo de nuevos materiales híbridos y sensors químicos más eficientes para aplicaciones biomédicas y terapeuticas.This PhD thesis entitled "Nanotechnology and supramolecular chemistry in controlled release and molecular recognition processes for biomedical applications", is focused on two important subjects: molecular recognition and controlled delivery processes. This PhD thesis is structured in four chapters. The first chapter introduces the concept of organic-inorganic hybrid materials containing switchable "gate-like" ensembles and their biomedical applications as nanomaterials for targeting and control drug delivery. Furthermore, is introduced a short review about chromo-fluorogenic chemosensors based on basic principles of supramolecular chemistry, particulary in molecular recognition processes. In particular, in chapter 2 is focus on the development of enzymatic-driven nanodevices. These hybrid materials are composed of two main units: an inorganic silica based mesoporous scaffold, able to store organic molecules and an organic compound anchored on the external surface of the inorganic mesoporous support than acts as molecular gate. All the systems proposed use peptidic gates that respond to temperature or enzimatic stimulis. The second part of this PhD thesis is focused on the design and development of a new chemical compound capable of detecting carbon monoxide in vivo. In summary, for all the results above mentioned we can say that this PhD thesis constitutes an original scientific contribution to the development of supramolecular chemistry. Its results derived from the studies presented leaves open routes to continue the study and development of new hybrid materials and more efficient chemical sensors with biomedical and therapeutic applications.
La present tesi doctoral, titulada "Nanotecnologia i química supramolecular en processos d'alliberament controlat i reconeixement molecular per a aplicacions biomèdiques", es centra en dos temes importants de la química: el reconeixement molecular i els processos d'alliberament controlat. Aquesta tesi doctoral està estructurada en quatre capítols. El primer capítol introdueix el concepte de materials híbrids orgànics-inorgànics funcionalitzats amb portes moleculars i les seves aplicacions biomèdiques com nanomaterials per dirigir i controlar l'alliberament controlat de fàrmacs. A més s'introdueix una breu descripció sobre sensors colorimètrics fonamentats en la base de la química supramolecular, particularment en els processos de reconeixement molecular. En particular, el capítol 2 descriu la preparació de cinc nanodispositius que responen a enzims. Aquests materials híbrids es componen de dues unitats principals: un suport mesoporos basat en sílice inorgànica, capaç d'encapsular molècules orgàniques i un compost orgànic ancorat a la superfície externa del suport mesoporós inorgànic que actua com a porta molecular. La segona part d'aquesta tesi doctoral es centra en el disseny i desenvolupaent d'un nou compost químic capaç de detectar monòxid de carboni in vivo. En resum, per a tots els resultats abans mencionats podem dir que esta tesi doctoral constituïx una contribució científica original al desenvolupament de la química supramolecular. Els seus resultats derivats dels estudis presentats deixen rutes obertes per a continuar l'estudi i el desenvolupament de nous materials hibrids i sensors químics més eficients per a aplicacions biomèdiques i terapeutiques.
De La Torre Paredes, C. (2017). Nanotechnology and supramolecular chemistry in controlled release and molecular recognition proceses for biomedical applications" [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/94043
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Dennis, Andrew C. "Studies of some molecular reorganisations in the solid state and in colloidal media by vibrational spectroscopy." Thesis, Queen's University Belfast, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.322846.
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Kwok, Connie Sau-Kuen. "Development of self-assembled molecular structures on polymeric surfaces and their applications as ultrasonically responsive barrier coatings for on-demand, pulsatile drug delivery /." Thesis, Connect to this title online; UW restricted, 2001. http://hdl.handle.net/1773/7999.
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Zhou, Chenguang. "NANOCARRIERS FOR THERAPEUTIC NUCLEIC ACID DELIVERY." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1336584204.
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Chen, Po Chih. "Design and synthesis of small molecules and nanoparticle conjugates for cell type-selective delivery." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/28111.
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Thesis (M. S.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2009.Committee Chair: Oyelere, Adegboyega; Committee Member: Bunz, Uwe; Committee Member: Collard, David; Committee Member: Lobachev, Kirill; Committee Member: Tolbert, Laren.
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Gade, Terence Peter Ferrante. "Integrated imaging of drug delivery : a molecular imaging approach to the optimization of cancer therapy /." Access full-text from WCMC:, 2007. http://proquest.umi.com/pqdweb?did=1432803381&sid=12&Fmt=2&clientId=8424&RQT=309&VName=PQD.
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Hernández, Teruel Adrián. "Smart drug delivery systems designed to improve Inflammatory Bowel Disease therapy." Doctoral thesis, Universitat Politècnica de València, 2019. http://hdl.handle.net/10251/129863.
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[ES] La presente tesis doctoral titulada "Sistemas de liberacio'n controlada de fa'rmacos diseñados para mejorar el tratamiento de Enfermedad Inflamatoria Intestinal" se centra en el diseño, preparación, caracterización y evaluación in vivo de distintos sistemas de liberación controlada de fármacos en colon (CDDS, por sus siglas en inglés) utilizando como soporte micropartículas de silice mesoporosa, funcionalizadas con puertas moleculares.
En conclusión, los estudios realizados demuestran que los materiales de silice mesoporosa, en combinación con puertas moleculares sensibles a estímulos específicos, tienen un gran potencial para el desarrollo de nuevos sistemas de liberación controlada de fármacos en el colon, dirigidos a mejorar el arsenal terapéutico disponible para el tratamiento de EII. La posibilidad de adaptar o personalizar la carga y las puertas moleculares hace que estos soportes de sílice mesoporosa sean una opción interesante para el desarrollo de nuevos sistemas de liberación controlada de fármacos en diferentes aplicaciones biomédicas. Finalmente, esperamos que los resultados obtenidos en esta tesis doctoral sirvan de inspiración para el desarrollo de sistemas de liberación controlada de fármacos innovadores y cada vez más inteligentes, para su aplicación tanto en medicina como en otras áreas.[CAT] La present tesi doctoral titulada "Sistemes d'alliberament controlat de farmacs dissenyats per a millorar el tractament de Malaltia Inflamatoria Intestinal" se centra en el disseny, preparacio, caracteritzacio i avaluacio in vivo de diferents sistemes d'alliberament controlat de farmacs en colon (*CDDS, per les seues sigles en angles) utilitzant com a suport microparticules de si'lice mesoporosa, funcionalitzades amb portes moleculars. En conclusio, els estudis realitzats demostren que els materials de si'lice mesoporosa, en combinacio amb portes moleculars sensibles a estimuls especifics, tenen un gran potencial per al desenvolupament de nous sistemes d'alliberament controlat de farmacs en el colon, dirigits a millorar l'arsenal terapeutic disponible per al tractament de MII. La possibilitat d'adaptar o personalitzar la carrega i les portes moleculars, fa que aquests suports de silice mesoporosa siguen una opcio interessant per al desenvolupament de nous sistemes d'alliberacio controlada de farmacs en diferents aplicacions biomediques. Finalment, esperem que els resultats obtinguts en aquesta tesi doctoral servisquen d'inspiracio per al desenvolupament de sistemes d'alliberament controlat de farmacs innovadors i cada vegada mes intel·ligents, per a la seua aplicacio tant en medicina com en altres arees.
[EN] This PhD thesis entitled "Smart drug delivery systems designed to improve Inflammatory Bowel Disease therapy" is focused on the design, synthesis, characterization and in vivo evaluation of several Colon Drug Delivery Systems (CDDS) using hybrid mesoporous silica microparticles as scaffolds containing molecular gates. In conclusion, the studies shown in this Thesis demonstrate that mesoporous silica materials in combination with responsive molecular gates have great potential in the design and preparation of new CDDS to improve the therapeutic options available for IBD. The possibility to adapt the cargo and the molecular gate makes mesoporous silica support especially appealing for similar controlled drug delivery applications in the biomedical field. We hope that the obtained results could inspire the development of new innovative smart drug delivery systems in this or other fields.
We thank the Spanish Government (projects MAT2015-64139-C4-1-R and AGL2015-70235-C2-2-R (MINECO/FEDER)) and the Generalitat Valenciana (project PROMETEOII/2014/047) for support. AHT thanks to the Spanish MEC for his FPU grant. We thank the Generalitat Valenciana (Project PROMETEO2018/024)
Hernández Teruel, A. (2019). Smart drug delivery systems designed to improve Inflammatory Bowel Disease therapy [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/129863
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Kaur, Davinder. "Investigation of cellular and molecular mechanisms involved in targeted drug delivery systems for human cancers." Thesis, University of Leicester, 2002. http://hdl.handle.net/2381/29670.
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CytocapsTM are a potential drug delivery system comprising of approximately 3-micron human serum albumin microcapsules with doxorubicin covalently linked to their outer surface. In the present study this drug delivery system was investigated in vitro using a combination of cytometric techniques including flow cytometry, Laser scanning cytometry, fluorescent microscopy and high performance liquid chromatography to investigate the binding of CytocapsTM and uptake of doxorubicin in both adherent (MCF-7/Wild type (WT), MCF-7/doxorubicin resistant (R) and EA.hy926) and non-adherent (HL-60 and Jurkat) cancerous cell lines. With all cells studied CytocapsTM appeared to act by releasing small amounts of drug which was taken up and then processed by the cells and responded in very similar ways to cell incubated with free drug. CytocapsTM bound to adherent cells (albeit to a sub-set of the population) but not non-adherent cell lines or peripheral blood cells. Whilst this study only investigated a limited number of cell types it would be logical to conclude that the binding of CytocapsTM to adherent cells was found to be generalised phenomenon. The efficacy of doxorubicin CytocapsTM was similar to free doxorubicin in terms of dosage. CytocapsTM were unable to overcome multiple drug resistance in the MCF-7/R cell line despite the entry of CytocapsTM into the cells at 72-168 hour incubations. Despite the different patterns of drug uptake in all the different cell types (excluding the MCF-7/R cells) comparable concentrations (0.5mM) of either CytocapsTM or free doxorubicin produced a predominantly cytostatic effect in the cells rather than a cytotoxic effect. In conclusion, CytocapsTM prove to be an effective mechanism for delivery of doxorubicin. Their interaction with adherent MCF-7/WT, MCF-7R and EA.hy926 cells could prove to be beneficial and could be used in the treatment of solid aggressive cancers where the CytocapsTM would be able to penetrate the different layers of cells by exerting their effect in the core of the tumour.
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Clergeaud, Veiga Gael. "Liposomes as versatile tools: nanoreactors, membrane models and drug delivery carriers." Doctoral thesis, Universitat Rovira i Virgili, 2014. http://hdl.handle.net/10803/285333.
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Les molècules lipídiques poden formar nombroses estructures supramoleculars a través de les seves propietats d’autoacoblament en ambients aquosos. Una de les estructures més explorades, els liposomes, son formades quan les bicapes lamelars s’encorben en vesícules tancades amb un nucli aquós al seu interior. Aquesta particular organització, que ofereix ambients hidrofílic (nucli) i hidrofòbic (dins de la membrana) per poder transportar molècules polars i apolars, juntament amb la seva naturalesa biocompatible, biodegradable i no immunogènica, fa que els liposomes siguin una de les pedres angulars de la nanobiotecnologia.
En conseqüència, els liposomes han estat àmpliament establerts com a eines versàtils en un gran nombre d’aplicacions, incloent productes farmacèutics, cosmètics, tecnologia dels aliments, com a models de membranes biològiques, com amplificadors de senyal en ciències analítiques, nanoreactors, eines de diagnòstic i un ampli etcètera.
En aquest treball hem demostrar l’ús dels liposomes com a nanoreactors o plantilles per la síntesis de nanopartícules metàl·liques de forma i mida controlada. A més, els liposomes també s’han utilitzat com a models de membrana que imiten la membrana plasmàtica de la cèl·lula per la determinació de la activitat ionòfora de diferents compostos fenòlics dietètics fins al zinc. Per últim, ha estat explorada la capacitat dels liposomes pel transport i la entrega de medicaments amb la finalitat de desenvolupar el potencial dels liposomes, sensibles a la degradació específica per un enzim, com a vehicles de fàrmacs per la encapsulació d’oxaliplatí pel tractament del càncer de colon. En resum, el treball presentat en aquesta tesi doctoral enforteix la visió dels liposomes com eines versàtils que poden ser utilitzades en diferents aplicacions científiques.Las moléculas lipídicas pueden formar numerosas estructuras supramoleculares gracias a sus propiedades de auto ensamblaje en ambientes acuosos. Una de las estructuras más exploradas, los liposomas, son formados cuando bicapas laminares se curvan produciendo vesículas cerradas con un núcleo acuoso en el interior. Esta particular organización, la cual ofrece ambientes hidrófilos (en el núcleo) e hidrófobos (dentro de la membrana) para poder transportar moléculas polares y apolares, junto con su naturaleza biocompatible, biodegradable y no inmunogenica, hace que los liposomas sean una de las piezas claves en el ámbito de la nanobiotecnologia. En consecuencia, los liposomas han sido ampliamente establecidos como herramientas versátiles en un gran número de aplicaciones, incluyendo productos farmacéuticos, cosméticos, tecnología de los alimentos, como modelos de membranas biológicas, amplificadores de señal en ciencias analíticas, nanoreactores, herramientas de diagnóstico y un amplio etcétera. En este trabajo hemos demostrado el uso de liposomas como nanoreactores o plantillas para la síntesis de nanopartículas metálicas de forma y tamaño controlada. Además, los liposomas también se utilizaron como modelos de membrana que imitan la membrana plasmática de la célula para la determinación de la actividad ionófora de varios compuestos fenólicos dietéticos hacia el zinc. Por último, la capacidad de los liposomas para el transporte y entrega de medicamentos ha sido explorada con el fin de desarrollar el potencial de liposomas que son sensibles hacia la degradación específica por una enzima como vehículos de fármacos para la encapsulación de oxaliplatino para el tratamiento del cáncer de colon. En resumen, el trabajo presentado en esta tesis doctoral fortalece la visión de los liposomas como herramientas versátiles que pueden ser utilizadas en diferentes aplicaciones científicas.
Lipid molecules can form numerous supramolecular structures through their self-assembly properties displayed within aqueous environments. One of the most explored structures, the liposomes, are formed when lamellar bilayers bend into closed vesicles containing an aqueous core inside. This particular structural organization, offering hydrophilic (core) and hydrophobic (within the membrane) environments to carry both polar and non-polar molecules,as well as their biocompatible, biodegradable and non-immunogenic properties, make liposomes as one of the cornerstones of nanobiotechnology. Consequently, liposomes have been extensively established as versatile tools in a large number of applications including pharmaceutics, cosmetics, food technology, models as biological membranes, signal amplifiers in analytical sciences, nanoreactors, diagnosing tools and a wide so on. In summary, the work presented in this doctoral thesis strengthens the view of liposomes as versatile tools that can be used in many different scientific applications. Liposomes were exploited as nanoreactors or templates for the shape and size controlled synthesis of metal nanoparticles. Furthermore, liposomes were used as membrane models that mimic the cell plasma membrane for the determination of zinc ionophore activity of several dietary phenolic compounds. Ultimately, the ability of liposomes to carry and delivery drugs was explored in order to investigate the potential of enzyme-degradable liposomes as drug carriers for the encapsulation of oxaliplatin to effectively enhance its pharmacokinetics for the treatment of colon cancer. In summary, the work presented in this thesis strengthens the vision of liposomes as a versatile tool that can be used in different scientific applications.
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Martini, Cecilia. "Idrotalciti Zn/Al intercalate con molecole biologicamente attive per il trattamento combinato di neoplasie." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2017. http://amslaurea.unibo.it/14432/.
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Le idrotalciti (HTlc), note anche come argille anioniche o idrossidi doppi lamellari, sono costituite da strati carichi positivamente con intercalati anioni di varia natura. Questo lavoro di tesi ha riguardato la sintesi e caratterizzazione di HTlc nanometriche con formula [Zn0,72Al0,28(OH)2] Br0,28•0,69H2O. Grazie allo loro biocompatibilità, stabilità e bassa tossicità, tali composti risultano particolarmente adatti alla veicolazione di farmaci. Pertanto, ho messo a punto la sintesi e intercalazione all’interno delle HTlc di due diverse sostanze: la norcantaridina (NCTD), una molecola organica antitumorale in grado di bloccare il ciclo cellulare in fase G2/M e la ftalocianina tetrasulfonata (ftl), una molecola fotosensibile anionica che illuminata a una specifica lunghezza d'onda, sviluppa sostanze citotossiche, quali specie radicaliche dell'ossigeno (ROS) e ossigeno di singoletto (1O2), in grado di uccidere le cellule malate. Questi nanocompositi, inoltre, sono stati caratterizzati in termini di capacità di loading e di rilascio nel tempo. Inoltre, sono stati effettuati test in vitro per valutare l’efficacia di questi composti su un panel di linee cellulari tumorali, ed è stato dimostrato che i farmaci caricati sulle HTlc sono più citotossici rispetto alle molecole libere, sia quando somministrati singolarmente che in combinazione.
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Bock, Nathalie. "Delivery of therapeutic molecules using electrosprayed polymeric particles for applications in tissue engineering." Thesis, Queensland University of Technology, 2014. https://eprints.qut.edu.au/74514/1/Nathalie_Bock_Thesis.pdf.
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This thesis has developed an innovative technology, electrospraying, that allows biodegradable microparticles to deliver pharmaceuticals that aid bone regeneration. The establishment, characterisation and optimisation of the technique are a step forward in developing an affordable and safe alternative to the products used currently in the clinical setting for the treatment of musculoskeletal disorders. The researcher has also investigated electrospraying as a coating technique on biodegradable structures that are used to replace damaged tissues, in order to provide localised and efficient drug delivery in the site of the defect to help tissue reconstruction.
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Eing, Matthias. "Polymeric nanocarriers for the visualisation and quantification of molecular release." Thesis, Queensland University of Technology, 2019. https://eprints.qut.edu.au/132683/1/Matthias_Eing_Thesis.pdf.
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This thesis is focused on the establishment on novel approaches towards drug release systems. The polymer-based nanocarriers presented herein are aimed at providing new building blocks for the highly controlled delivery of drug molecules towards tissue. A variety of triggers to facilitate the efficient release of the drug at the site including physiological factors and the utilisation of blue light are explored. In addition, a modern approach towards the visualisation of effective release is demonstrated. Fluorescence is used as a universal indicator to quantify the efficiency of release.
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Orellana, Bryan R. "BIOERODIBLE CALCIUM SULFATE BONE GRAFTING SUBSTITUTES WITH TAILORED DRUG DELIVERY CAPABILITIES." UKnowledge, 2014. http://uknowledge.uky.edu/cbme_etds/18.
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Bone regeneration or augmentation is often required prior to or concomitant with implant placement. With the limitations of many existing technologies, a biologically compatible synthetic bone grafting substitute that is osteogenic, bioerodible, and provides spacing-making functionality while acting as a drug delivery vehicle for bioactive molecules could provide an alternative to ‘gold standard’ techniques.
In the first part of this work, calcium sulfate (CS) space-making synthetic bone grafts with uniformly embedded poly(β-amino ester) (PBAE) biodegradable hydrogel particles was developed to allow controlled release of bioactive agents. The embedded gel particles’ influence on the physical and chemical characteristics of CS was tested. Namely, the compressive strength and modulus, dissolution, and morphology, were studied. All CS samples dissolved via zero-order surface erosion consistent to one another. Compression testing concluded that the amount, but not size, of embedded gel particles significantly decreased (up to 75%) the overall mechanical strength of the composite. Release studies were conducted to explore this system’s ability to deliver a broad range of drug types and sizes. Lysozyme (model protein for larger growth factors like bone morphogenic protein [BMP]) was loaded into PBAE particles embedded in CS matrix. The release of simvastatin, a small molecule drug capable of up regulating BMP production, was also examined. The release of both lysozyme and simvastatin was governed by dissolution of CS.
The second part of this work proposed a bilayered CS implant. The physical and chemical properties were characterized similarly to the CS composites above. Release kinetics of directly loaded simvastatin in either the shell, core, or both were investigated. A sequential release of simvastatin was witnessed giving foresight of the composite’s tunability. The sequential release of an antibacterial, metronidazole, loaded into poly(lactic-co-glycolic acid) (PLGA) particles embedded into the shell along with directly loaded simvastatin either in the shell, core, or both layers was also observed. Through controlled release of bioactive agents, as well as a tunable layered geometry, CS-based implants have the potential to be optimized in order to help streamline the steps required for the healing and regeneration of compromised bone tissue.
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Nagireddy, Bharat. "AN EFFECTIVE DRUG DELIVERY PROCESS USING A NOVEL CYLINDRICAL PARTICLE MODEL JUSTIFIED BY MOLECULAR DYNAMICS SIMULATION." University of Akron / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=akron1187105640.
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Bareiss, Bettina. "Development of in vitro Models for Delivery of the Anti-Viral Drug Acyclovir for Ocular HSV-I Infection Treatment." Thesis, University of Ottawa (Canada), 2010. http://hdl.handle.net/10393/28542.
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Herpes simplex virus 1 (HSV-1) infection is the main cause of vision loss in the developed world due to the fact that after initial infection, the virus establishes latency and can be reactivated; resulting in a very low success rate of treatment by transplantation (22%). We are developing corneal substitutes suitable for HSV-1 transplantation by incorporating anti-viral drugs such as acyclovir (ACV), into corneal substitutes that could potentially suppress the viral reactivation. Specifically, we examined the feasibility of preventing viral reactivation during surgery, by sustained delivery of ACV introduced during corneal transplantation surgery, through encapsulation of the drug within silica (SiO2) nanoparticles (NP) incorporated into biosynthetic alternatives to donor corneas. We show that incorporation of NPs did not affect optical clarity of the collagen-based corneal substitutes nor their biocompatibility. NP-encapsulation effectively sustained ACV release from the biosynthetic implants over 10 days, compared to free ACV incorporated directly into the hydrogel constructs. The NP-enabled sustained release resulted in effective prevention of virally-induced cell death, not observed with the free drug. This early model demonstrates the feasibility of using biomimetic corneal substitutes that incorporate a drug release system (e.g. silica nanoparticles encapsulating ACV) as future alternatives to human donor tissue grafts, for transplantation of HSV-infected corneas.
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Abdullah, Che Azurahanim Che. "Nanostructured materials as molecular transporters and cell growth substrates for drug delivery and tissue engineering applications." Thesis, University of Surrey, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.548355.
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Llorens, Domenjó Elena. "Advanced electrospun scaffolds based on biodegradable polylactide and poly(butylene succinate) for controlled drug delivery and tissue engineering." Doctoral thesis, Universitat Politècnica de Catalunya, 2014. http://hdl.handle.net/10803/284662.
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Electrospinning is a manufacturing process that uses an electric field to produce fibers from a polymer solution. The accumulation of these fibers conform a three-dimensional fiber matrix or scaffold. Fibers can be prepared in a wide diameter range, namely from a micrometer to nanometer size. Furthermore, the fiber matrix or scaffold has a large surface per mass unit, a porous structure and mechanical properties influenced by the orientation of the fibers.
The electrospinning technique is highly versatile and therefore a large number of polymers with different properties can be processed. However, a large number of variables can influence the characteristics of the resulting fibers, either because they are related to the polymer properties (e.g., solubility, molecular weight, etc.) or with the specific processing parameters (voltage, flow rate or distance tip-collector). Electrospun fiber matrices are attractive for biomedical applications as for example tissue engineering and drug delivery systems. In the last case, it is important the possibility to load the fibers with different drugs for their direct and localized administration into the human body.
The goal of this Thesis is the study of different matrices constituted by electrospun micro- nanofibers and specifically four points have been considered. In the first one, polylactide electrospun scaffolds have been loaded with different molecules with antioxidant activity (i.e., vitamin B6 in pyridoxine and pyridoxal forms, p-coumaric acid and caffeic acid). The influence of these molecules on physical properties, morphology, in vitro release profiles and biocompatibility was determined. Furthermore, the application of these new materials for the inhibition of oxidative DNA damage caused by free radical initiators was demonstrated, and consequently, they appear appropriate candidates for purification of plasmidic or genomic DNA.
In the second point, PLLA matrices loaded with two or three drugs were prepared in order to get a multifunctional activity. Thus, antioxidant, anti-inflammatory and antimicrobial molecules were considered in order to prevent chain oxidation processes in different biomolecules (proteins, DNA, etc.), avoid the subsequent local inflammation, and reduce the potential risk of microbial infection of wounds, respectively. These matrices are especially interesting due to the synergies and antagonisms that may occur during their simultaneous release.
In the third point, the possibility of preparing biodegradable scaffolds from non electrospinable polymers has been considered. These polymers may have advantages like conductivity/electroactivity or bactericide activity. Hybrid scaffolds constituted by different ratios of polylactide as a biodegradable polymer and (poly(3-thiophene methyl acetate)) as electroactive polymer were evaluated. PLA nanofibers were also successfully loaded with polyhexamethylenebiguanide hydrochloride giving rise to 3D biodegradable scaffolds with a well proven antibacterial activity and a release that was highly dependent on the hydrophilicity of the medium.
Finally electrospun scaffolds were obtained using a sacrificial polymer (e.g. poly(ethylene glycol) (PEG)) that could easily be subsequently removed by solubilization in aqueous media. Three approaches were evaluated: a) Preparation of scaffolds constituted by different ratios of PLA and PEG electrospun fibers, b) Preparation of scaffolds constituted by electrospun fibers with different PLA and PEG content; c) Preparation of scaffolds constituted by coaxial electrospun fibers with different core-shell polymer distributions. Cell colonization was in all cases favoured. The three procedures allowed preparing scaffolds with a differentiated drug release behavior.La técnica de 'electrospinning' o electrohilado es un proceso de fabricación que utiliza un campo eléctrico para producir fibras a partir de disoluciones de polímeros. La acumulación de estas fibras conforma una matriz tri-dimensional o 'scaffold', y las fibras pueden ser preparadas en escala micro y nanométrica. Además, estas matrices o 'scaffold' se caracterizan por su gran superficie por unidad de masa, estructura porosa y propiedades mecánicas influenciadas por la orientación de las fibras. El 'electrospinning' es muy versátil y un gran número de polímeros con diferentes propiedades pueden ser procesados. Sin embargo, un gran número de variables pueden influir en las características de las fibras obtenidas, siendo variables propias del polímero (p.e., solubilidad, peso molecular, etc.) o relacionadas a los parámetros del proceso (voltaje, flujo, distancia colector-aguja). Estas matrices de fibras son atractivas para aplicaciones biomédicas como la ingeniería de tejidos y sistemas de liberación controlada de fármacos. En el último caso, es importante la carga de diferentes fármacos o drogas para su administración directa y localizada en el cuerpo humano. El objetivo de esta Tesis es el estudio de diferentes matrices constituidas por nano o microfibras electrohiladas. El desarrollo de este estudio se divide en cuatro bloques. En el primer bloque, matrices de fibras de poliláctico (PLA) fueron cargadas con diferentes moléculas con actividad antioxidante (vitamina B6 en sus formas de piridoxina y piridoxal, ácido p-cumárico y ácido cafeico). Se determinó la influencia de estas moléculas sobre las propiedades físicas, morfología, liberación in vitro y biocompatibilidad de dichas matrices. Además, se demostró la aplicación de estos nuevos materiales en la inhibición del daño oxidativo del ADN causado por iniciadores de radicales libres, y en consecuencia, estas matrices serían útiles para la purificación de ADN plasmídico o genómico. En el segundo bloque, las matrices de PLA fueron cargadas con dos o tres fármacos para obtener matrices multifuncionales en base a sus actividades. Con esta finalidad, moléculas con actividad antioxidante, anti-inflamatoria, y antimicrobiana fueron cargadas en las matrices para evitar los procesos de oxidación de diferentes biomoléculas (proteínas, ADN, etc.), evitar la inflamación local, y reducir el riesgo potencial de infección microbiana de las heridas, respectivamente. Estas matrices son especialmente interesantes debido a las sinergias y antagonismos que pueden ocurrir durante su liberación simultánea. En el tercer bloque, se prepararon matrices biodegradables a partir de polímeros no-electrohilables. Estos polímeros pueden presentar características particulares, como actividad bactericida, o actividad conductora/electroactividad. Matrices hibridas conformadas con diferentes ratios de PLA usado como polímero biodegradable y el poli(3-tiofeno metil acetato) como polímero electroactivo fueron preparadas y evaluadas. También se prepararon matrices de nanofibras de PLA cargadas con clorhidrato de polihexametilenbiguanida (PHMB) obteniéndose matrices biodegradables con actividad antibacteriana, y la liberación del PHMB fue altamente dependiente de la hidrófilicidad del medio. Finalmente, en el cuarto bloque, se prepararon matrices electrohiladas usando un polímero de sacrificio (polietilenglicol o PEG) que puede ser eliminado fácilmente por solubilización en medios acuosos. Tres preparaciones diferentes fueron evaluadas: a) Matrices constituidas por diferentes proporciones de PLA y PEG en las fibras, b) Matrices constituidas por fibras de PLA y fibras de PEG y, c) Matrices constituidas por fibras coaxiales con diferentes distribuciones de polímeros en el núcleo y la corteza de la fibra. La colonización celular en todas estas matrices fue mejorada. Estos tres procedimientos permitieron obtener matrices con diferentes comportamientos para la liberación de fármacos.
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Ramachandran, Niraj. "Corona Ion Deposition: A Novel Non-Contact Method for Drug and Gene Delivery to Living Systems." [Tampa, Fla] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002474.
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