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Mishra, Kaushik. « Folate Receptor-Targeted Polymeric Micellar Nanocarriers as Drug Delivery Systems ». University of Akron / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=akron1629218263972419.
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Rosenbaum, Erik. « Optical characterization of potential drugs and drug delivery systems ». Doctoral thesis, Umeå universitet, Kemiska institutionen, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-40177.
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This Thesis is a characterization study on substances having potency as drugs as well as on a lipid based drug-delivery matrix. The optical properties of newly synthesized molecules with proven pilicide properties have been characterized with several spectroscopic methods. These methods include optical absorption and fluorescence as well as time-resolved fluorescence. Upon covalently linking compounds with high quantum yields of fluorescence to specific parts of the pilicide, the biological impact was found to increase for some of the derivatives. Furthermore, by expanding the aromatic part of the pilicide molecule, a significant increase in the inherent fluorescence was obtained. The S0-S1 absorption band for these molecules was found to originate from an impure electronic transition, vibronically promoted by intensity borrowing from higher electronic states. Included in this Thesis is the measurement of how deeply some in this class of newly synthesized molecules become situated when placed inside ganglioside GM1 micelles, and how the molecules’ reorientation is affected. By means of radiation-less energy transfer, it was shown that the molecules place themselves close to the hydrophobic-hydrophilic interface inside the GM1 micelles. As a consequence they are exposed to a densely packed environment, which inhibits the free tumbling of the molecule. This restricted tumbling could be measured by means of time-resolved depolarization experiments. The release of drug-like fluorescent molecules is investigated from a lipid mixture, which upon equilibrium with water forms a mixture of inverted hexagonal and cubic phases. The lipid matrix displayed an extended release over the course of weeks, in vitro, for molecules having a large variation in hydrophobicity.
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Sutton, Damon Michael. « PH SENSITIVE RNA AND DRUG DELIVERY SYSTEMS ». Case Western Reserve University School of Graduate Studies / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=case1179847644.
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Zeng, Yi. « Stable Polymer Micelle Systems as Anti-cancer Drug Delivery Carriers ». Diss., CLICK HERE for online access, 2005. http://contentdm.lib.byu.edu/ETD/image/etd841.pdf.
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Hans, Meredith L. Lowman Anthony M. « Synthesis, characterization, and application of biodegradable polymeric prodrug micelles for long-term drug delivery / ». Philadelphia, Pa. : Drexel University, 2006. http://dspace.library.drexel.edu/handle/1860/741.
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SCIALABBA, Cinzia. « Nanosistemi polimerici per la veicolazione di farmaci antitumorali o attivi sul sistema nervoso centrale ». Doctoral thesis, Università degli Studi di Palermo, 2014. http://hdl.handle.net/10447/90804.
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Ponta, Andrei G. « POLYMER MICELLES FOR TUNABLE DRUG RELEASE AND ENHANCED ANTITUMOR EFFICACY ». UKnowledge, 2013. http://uknowledge.uky.edu/pharmacy_etds/26.
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Cancer remains a leading cause of death in the United States. The most common treatment options include chemotherapy, but poor solubility, adverse side effects and differential drug sensitivity hamper clinical applications. Current chemotherapy generally aims to deliver drugs at the limit of toxicity, assuming that higher dosage increases efficacy, with little attention paid to potential benefits of tunable release. Growing evidence suggests that releasing drugs at a constant rate will be as effective as a single bolus dose. To test this hypothesis, it is critical to develop drug delivery systems that fine-tune drug release and elucidate the impact of tunable drug release rates on chemotherapeutic efficacy.
Block copolymer micelles, spherical nanoassemblies with a core-shell structure, are widely used in recent research. Micelles for this study were engineered to release a model drug (doxorubicin: DOX) at differential rates under acidic conditions, corresponding to tumor tissue (pH < 7). Three specific aims were pursued: to develop drug carriers capable of tuning drug release rates; to determine activity of developed carriers in vitro; and to elucidate effects of tunable drug release rates in vivo.
Block copolymers with covalently linked DOX were synthesized and self-associated, forming micelles. Drug binding linkers (glycine, aminobenzoate, or hydrazide) were used to tune release of DOX. Micelles were characterized to determine physicochemical properties such as particle size, drug entrapment yields, and drug release parameters. Characterization revealed that drug release profiles were modulated by interchanging drug binding linkers.
Micelles were evaluated in vitro to elucidate the effect of tunable drug release. Micelles delivered drugs at a slower, prolonged rate compared to free DOX. Cytotoxicity and cellular internalization analysis revealed that by slowing release rates, micelles kill cells more efficiently.
Biodistribution studies showed that micelles decrease DOX accumulation in peripheral tissue while increasing the maximum tolerated dose. Antitumor activity studies verified that micelles with slower release rates better suppressed tumor growth. This further confirms that release rates play a key role in chemotherapeutic efficacy.
Therefore, this thesis provides better insights into the effects of tunable drug release in tumors, leading the way for improved chemotherapy treatments in the future.
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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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Raj, April. « Mechanistic studies to evaluate the targeting specificity of novel RGD Micelles to the αVβ3 integrin receptor ». Scholarly Commons, 2012. https://scholarlycommons.pacific.edu/uop_etds/830.
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Current chemotherapeutics pose many di sadvantages due to their lack of specificity and low therapeutic index. To overcome these challenges, research has focused its attention on the development of nano-based delivery systems that can penetrate the leaky vasculature of tumor endothelium, use site-directed ligands that can bind with high affinity and specific ity to tumor cells, physically entrap poorly soluble drugs, and deliver these cytotoxic agents directly to the tumor site. One approach to nanosystem drug delivery is with the use of peptide amphiphiles (PAs) that are conjugated with the Arginine-Glycine-Aspartic Acid (RGD) motif to actively target a αVβ3 integrin receptors on cancer cells or tumor endothelium. The current work is focused on mechanistic studies to evaluate the uptake of novel RGD amphiphi les with varying alkyl chain lengths (palmitic acid : Cl 6 and stearic acid: C 18) and hydrophilic linkers, 8-amino- 3,6-dioxaoctonoic acid (ADA) or glucose, as micellar delivery systems of hydrophobic anticancer agents. PAs were confirmed for their self-assembling properties and further evaluated for their RGD-mediated binding specificity to purified αVβ3 integrin through a competitive binding fluorescence polarization assay (with novel RGD micelles displacing an integrin-bound fluorescent RGD probe by as much as 63.03%). Ultimately, these nanocarriers were assessed for their ability to deliver phys ically entrapped fluorescein isoth iocyanate (FITC) to A2058 cells overexpressing αVβ3 integrin receptors. Results from confocal microscopy indicate that uptake of RGD micelles was driven by an energy-dependent mechanism, as statistically significant levels of FITC internalization was seen at 37°C versus 4°C (p-value<0.05 for all treatment groups); moreover, intracellular fluorescence was notably higher (as much as 4-fold) when delivered through novel RGD conjugates as opposed to its free form. Regardless of chain length and the number of hydrophilic linkers, all RGD PAs showed promising results as micellar carriers that can effectively deliver their payload to the target tumor site via receptor mediated endocytosis.
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Staples, Bryant J. « Pharmacokinetics of Ultrasonically-Released, Micelle-Encapsulated Doxorubicin in the Rat Model and its Effect on Tumor Growth ». Diss., CLICK HERE for online access, 2007. http://contentdm.lib.byu.edu/ETD/image/etd1844.pdf.
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Varvarenko, S. M., N. V. Puzko, A. S. Voronov, I. A. Dron, I. T. Tarnavchyk, N. G. Nosova, V. Ja Samaryk et S. A. Voronov. « Colloidal and Chemical Properties of Polyesters Based on Glutamic Acid and Diols of Different Nature ». Thesis, Sumy State University, 2012. http://essuir.sumdu.edu.ua/handle/123456789/35074.
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The paper describes synthesis method and colloid-chemical properties of novel α-amino acid based polyesters
with controllable hydrophilic-lipophillic balance. Glutamic acid and diols of different nature based
polyesters were obtained via low-temperature activated polyesterefication. Such polymers are able to form
micellar structures in self-stabilized water dispersion. Solubilization of water insoluble dyes Sudan and
toluene in polymer water solution was studied. Due to micelle forming ability and prognosticated biodegradability
to non-toxic products, obtained polymers are promising materials for formation of novel dispersed
drug delivery systems.
When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/35074
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Shen, Steve I. « Arg-Gly-Asp (RGD) conjugated aliphatic acids as micellar drug carrier for targeted drug delivery ». Scholarly Commons, 2004. https://scholarlycommons.pacific.edu/uop_etds/2641.
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Targeted drug delivery is desired in cancer therapy since most of the side effects common to chemotherapy are related to the toxicity of the drug. Integrin over-expression has been shown in various cancer cells and can be exploited for targeted drug delivery. The goal of this study is to design amphiphilic conjugates with targeting motifs as a targeted drug delivery carrier. Toward this effort, novel amphiphilic conjugates of the Arg-Gly-Asp (RGD) peptide or GRGDS was linked to aliphatic acids of varying chain length. The hypothesis is that these novel amphiphilic conjugates, at concentrations above the critical micelle concentration (CMC), can form micelles in aqueous environment, encapsulate poorly-water soluble drugs, and target the α v β 3 integrin. The amphiphilic conjugate is also hypothesized to serve as targeting moiety in mixed micelle drug delivery system using Pluronic block copolymer. Synthesis of RGD amphiphilic conjugates was achieved by converting carboxylic acids into more reactive N-hydroxysuccinimidyl derivative and converting the carboxylic functional group of peptide into methyl ester. Then the activated NHS aliphatic ester was conjugated with methyl-protected peptide in the presence of organic base and methyl ester was removed in NaOH and subsequently neutralized. Intermediates and final products were characterized by MS, FTIR, and NMR. Micelle formation occurred in concentration of 0.015 to 0.12 mM for C 14 -RGD, C 16 -RGD, C 18 -RGD, and C 18 -GRGDS. Amphiphilic conjugate mixed with Pluronic L121 and Pluronic P104 (5% C 18 -RGD/L121 and 10% C 18 -GRGDS/P104) formed micelles at lower CMC of 0.0006 and 0.01 mM, respectively. Solubility of Taxol in water was improved by 87% when encapsulated in C 18 -RGD micelle above CMC. The solubility was increased 7 fold and 18 fold in mixed micelles of 5% C 18 -RGD/P104 and 5% C 18 -RGD/L121 above CMC. Three different drugs (DOX, Taxol, and etoposide) were used to evaluate the efficacy of the targeting C 18 -GRGDS micelle carrier alone or C 18 -RGD mixed with Pluronic block copolymers micelle. All 3 drugs significantly enhanced cytotoxicity toward cancer cells when loaded in micelle carrier above CMC. With same DOX concentration, C 18 -GRGDS micelle carrier significantly decreased percent of viable cells (12.9 ± 1.2%) above CMC when compared to concentrations below CMC (24.1 ± 1.0%). Mixed micelle of targeting amphiphile and Pluronic loaded with Taxol above CMC significantly decreased the percent of viable cells (38.3 ± 7.9%) when compared to non-targeting Pluronic block copolymer micelle (56.0 ± 2.8%). (Abstract shortened by UMI.)
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Ketkar, Amol Sharad. « Polymeric drug delivery systems / ». The Ohio State University, 1994. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487859879937796.
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Zaher, Amir. « Remotely controlled drug delivery systems ». Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/57611.
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Implantable drug delivery is becoming an increasingly important field of research, providing great potential for a wide range of flexible and low cost solutions for localized treatment of chronically debilitating diseases. This dissertation presents work that encompasses several approaches for the remote triggering, powering, and control of micro drug delivery devices and systems, designed with remote-controllability, minimal power requirements, biocompatibility, and the potential for minimally invasive implantation in mind. The control mechanisms used rely on microtechnology, nanotechnology, and electromagnetic power transfer to magnetic nanoparticles and magnetic nanowires, for the heating and actuation of thermoresponsive Poly(N-isopropylacrylamide) hydrogels (PNIPAm) in the form of nanoparticles in membranes and stand-alone microdroplets, and actuation of flexible membranes for drug pumping. Thermoresponsive PNIPAm, in any form such as nanoparticles, microdroplets, or mezzo scale bulk material shapes, has the property of swelling with water in its hydrophilic state below a critical temperature. At higher temperatures, a sharp change occurs, the polymer network becomes hydrophilic, and the water molecules in the network is expelled, causing the overall material to shrink in size, while the released water or aqueous solution is left free to flow around or away from the material. When embedded in membrane matrices used as drug delivery gates, PNIPAm nanoparticles act as diffusion and flow blockers below the critical temperature. When PNIPAm surpasses the critical temperature, induced by heat from local magnetic iron oxide nanoparticles (exposed to a 62 mT, 450 kHz magnetic field), it shrinks in size and increases the drug flow through membrane pathways. The combination of this membrane design with osmotic pumping and methods for tailoring the drug release profile is reported. Simulation supports experimental results while describing interactions between the osmotic pump and the thermoresponsive membranes. A sensitivity analysis based on a fluidic circuit analogy gives insight into the contributions of the components of the device, in particular those of membranes affecting the displacement of fluid. PNIPAm microdroplets, spherical microparticles larger than the PNIPAm nanoparticles discussed above, are fabricated with embedded magnetic iron oxide nanoparticles or magnetic iron nanowires and pre-loaded with an aqueous drug. Upon magnetic heating, these microdroplets shrink in size and expel the drug. Magnetic nanowires have much lower power requirements when compared with widely-used iron oxide magnetic nanoparticles for triggering PNIPAm, due to their ability to generate losses via physical vibration within the microdroplets. A model is used to corroborate the experimentally observed low power (1 mT, 20 kHz magnetic field) required to induce PNIPAm microdroplet shrinkage. This model for nanowire loaded microdroplet design is compared with the well-established theory for power generation from magnetic iron oxide nanoparticles, and associated experiments (using a 72 mT, 600 kHz magnetic field) in order to confirm the validity of the calculated power generated by iron nanowires. The findings in this work offer several flexible options for the application of PNIPAm as a remotely triggerable drug delivery controller or carrier, using relatively simple fabrication methods, permitting several degrees of customization of the delivery rate or profile by adjusting the PNIPAm material, its magnetic content, and the applied magnetic field, all the while demonstrating the use of magnetic nanowires as a more efficient power transfer material when compared to traditionally used magnetic nanoparticles. The findings associated with the efficient triggering of PNIPAm microdroplets can be implemented in a more power-friendly design of magnetic, remotely triggered membranes which, although implemented in conjunction with osmotic pumps here, can be coupled with other pressure sources.Applied Science, Faculty of
Engineering, School of (Okanagan)
Graduate
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Squire, Marie A. « Protein-based drug delivery systems ». Thesis, University of Canterbury. Chemistry, 2004. http://hdl.handle.net/10092/6518.
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The targeted delivery of drugs is one of the most actively pursued goals in anti-HIV and anti-cancer chemotherapy. This project takes a proof-of-concept approach to the development of protein-based drug delivery systems - delivery systems that would package, target, and deliver cytotoxins to diseased cells.
Primarily, this project explores the use of the potent anti-HN protein, cyanovirin-N (CV-N), to actively target and deliver cytotoxic natural products to HN-infected cells. This project also investigates the use of human serum albumin (HSA), a 66 kDa protein, as a macromolecular carrier to passively target and deliver cytotoxic natural products to cancerous cells.
To facilitate release of the toxin within infected cells, an enzymatically-cleavable tetra peptide was incorporated in the conjugates. Maleimido-activated tetra peptide toxin constructs were prepared in readiness for selective reaction with proteins carrying thiol functionalities. Release of the toxin, norhomohalichondrin B, was demonstrated in vitro.
Native CV -N conjugates were prepared by thiolation of the lysine ε-amino groups, and the subsequent reaction with maleimido-activated compounds. Reaction across all lysine residues was demonstrated. A singly-substituted tyrosinamide conjugate of CV-N was prepared. Two recombinantly produced mutant CV-N proteins allowed for the production of selectively modified, double- and single-norhomohalichondrin B conjugates of CV-N. The conjugates retained the anti-HN activity of the parent protein.
Homohalichondrin B, doxorubicin, and tyrosinamide conjugates of HSA were prepared. The syntheses exploited the availability of a free thiolmoiety at cysteine-34 of HSA, and the specific and selective reaction of this thiol with the maleimido-activated tetra peptide derivatives.
All toxin conjugates demonstrate excellent cell toxicity. Further research to investigate whether this is targeted toxicity is currently underway.
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Muldoon, B. M. « Mucoadhesive systems for drug delivery ». Thesis, Queen's University Belfast, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268336.
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Allen, Rosamund Elizabeth. « Liposomes as drug delivery systems ». Thesis, University of Essex, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.352982.
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Qin, Jian. « Environment-Sensitive Multifunctional Drug Delivery Systems ». Doctoral thesis, KTH, Funktionella material, FNM, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-12053.
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Drug delivery systems (DDS) with multiple functionalities such as environment-sensitive drug release mechanisms and visualization agents have motivated the biomedical community as well as materials chemists for more than a decade. This dissertation is concerned with the development of nanoparticles for multifunctional DDS to tackle several crucial challenges in these complex systems, including polymeric nanospheres which respond to temperature change, superparamagnetic iron oxide nanoparticles/polymeric composite for magnetic resonance imaging contrast agents and drug carriers, immunoresponse of nanomaterials and injectable magnetic field sensitive ferrogels. The biocompatible and biodegradable polylactide (PLA) was employed as matrix materials for polymeric nanosphere-based DDS. The thermosensitive polymeric nanospheres have been constructed through a “modified double-emulsion method”. The inner shell containing the thermosensitive poly(N-isopropylacrylamide) (PNIPAAm) undergoes a “hydrophilic-to-hydrophobic” phase transition around the human body temperature. The sensitivity of the polymer to the temperature can facilitate drug release at an elevated temperature upon administration. In addition, gold nanoparticles were assembled on the dual-shell structure to form a layer of gold shell. The cell viability was found to be enhanced due to the gold layer. The immunoresponse of the gold nanoparticles has been considered even if no acute cytotoxicity was observed. Imaging is another functionality of multifunctional DDS. This work focuses on magnetic resonance imaging (MRI) and involves synthesis and surface modification of superparamagnetic iron oxide nanoparticles (SPIONs) for contrast agents. The SPIONs have been prepared through a high temperature decomposition method. Surface modification was carried out in different ways. Poly(L,L-lactide) (PLLA) was grafted on SPIONs through surface-initiated ring-opening polymerization. The hydrophobic model drug indomethacin was loaded in the PLLA layer of the composite particles. For biomedical applications, it is essential to modify the hydrophobic particles so that they can be dispersed in physiological solutions. A series of protocols including using small charged molecules and amphiphilic polymers has been established. Pluronic F127 (PF127), a triblock copolymer was applied as a phase transfer reagent. Most interestingly, PF127@SPIONs show remarkable efficacy as T2 contrast agents. The PF127@SPIONs have been successfully applied to image the cochlea in a rat model. As another phase transfer reagent, poly(maleic anhydride-alt-octadecene)-graft-PNIPAAm (PMAO-graft-PNIPAAm) was created for surface modification of SPIONs. This new copolymer provides the modified SPIONs with thermosensitivity together with water-dispersibility. As another form of DDS, ferrogel made of PF127 copolymer and SPIONs was developed. Gelation process depends on the temperature of the SPIONs/PF127 mixture. This property makes it possible to use the ferrogel as an injectable drug carrier. Unlike other ferrogels based on crosslinked polymeric network, the PF127 ferrogel can entrap and release hydrophobic drugs. Application of an external magnetic field is found to enhance the drug release rate. This property can find application in externally stimulated local drug release applications.QC20100722
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Qin, Jian. « Nanoparticles for multifunctional drug delivery systems ». Licentiate thesis, Stockholm : Kemi, Kungliga Tekniska högskolan, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-4369.
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Campbell, K. C. « Novel systems for transdermal drug delivery ». Thesis, Queen's University Belfast, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368758.
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Lee, Antony James. « Mathematical modelling of drug delivery systems ». Thesis, University of Nottingham, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309563.
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Udo-Chijioke, Onyinyechi. « Aquasomes : multilayered nanoparticular drug delivery systems ». Thesis, Aston University, 2016. http://publications.aston.ac.uk/33399/.
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Nanoparticulate delivery systems have been widely used in recent decades, available in a wide variety of structures, for targeted drug delivery. They provide controlled and prolonged release for drugs, peptides and biopharmaceuticals. Ceramic nanoparticles are one of the various nanocarriers, which have been employed in local targeted delivery, most commonly in the area of orthopaedic drug delivery to enhance treatment therapies. This thesis therefore focused on the development of aquasomes, a ceramic nanoparticulate carrier system, for the delivery of proteins, growth factors and antibiotics for its potential application in bone regeneration in fracture healing. The suitability of non-aqueous silicone elastomer gels (NASEGs) as a topical/transdermal delivery system for proteins as well as protein-loaded aquasomes was also investigated. Through process optimisation, a suitable lyophilisation method was developed and used for the preparation of bioactive aquasome formulations of growth factors, bone morphogenetic protein (BMP-2), vascular endothelial growth factor (VEGF-121), and antibiotic, gentamicin. Physical characterisation of aquasomes using zeta potential and optimisation of preliminary aquasome formulations were optimised by utilising smaller nanocore sizes. In addition, scanning electron microscopy (SEM), confocal microscopy analysis and entrapment efficiency studies were performed to ascertain the drug loading efficiency of the different aquasome formulations. BMP-2 loading aquasomes exhibited an entrapment efficiency of 98.9% Protein loading on aquasomes yielded a higher negative zeta potential in comparison to blank nanocores. Confocal microscopy images elucidated the behaviour of nanocore particles showing agglomeration of nanocores and the presence of fluorescent drug adsorbed onto nanocores. The bioactivity of the aquasome formulations were analysed via in vitro cell culture model assays and microbiological assays. BMP-2-loaded aquasomes were investigated for enhanced osteogenic proliferation and differentiation effects on osteoblast-like cells, MG63 cells. The enhanced osteogenic effect of HUVECs in co-culture with these cells was also examined. In addition, the committed differentiation of ATMSCs into osteoblasts induced by their exposure to BMP-2 -loaded aquasomes was also investigated. Results exhibited the enhanced osteogenic differentiation effect, analysed by alkaline phosphatase (ALP) secretion (a major biochemical marker of osteoblastic differentiation) from MG63 cells was dependent on the protein loading onto the aquasome formulation. However, differentiation of ATMSCs cultured in osteogenic medium was significantly higher than ATMSCs exposed to BMP-2 or VEGF-121 treatments. Gentamicin-loaded aquasomes were investigated for their antimicrobial activity against Staphylococcus aureus, a major pathogen popularly implicated in cases of osteomyelitis. Results showed that gentamicin released from aquasomes exhibited excellent bactericidal activity against bacterial cultures without any reproduction of bacteria in 24 hours. In conclusion, the aquasome formulations were able to offer controlled release of bioactive antimicrobials and growth factors over a prolonged duration. The amount of bio-actives released was dependent on the loading of the bio-actives in the fabrication process of aquasome formulations. However, minute (ng/μg) amounts of adsorbed growth factor/drug were observed in comparison to the loading (high ng/mg) within the duration of study. It can be inferred these aquasomes can be employed in the sustained local and targeted delivery of antimicrobials and growth factors in orthopaedic treatments for enhanced fracture healing. However, the loading of bio-actives onto aquasome formulations may need to be optimised to increase the amount of bio-actives released to elicit more pronounced pharmacological effects.
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Weaver, Richard. « Polyammonium conjugates as drug delivery systems ». Thesis, University of Leicester, 1995. http://hdl.handle.net/2381/33980.
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This thesis describes the novel synthesis of eight polyamine-nitrogen mustard conjugates and two polyamine-nitroxide conjugates. The structure-activity relationship of these compounds with DNA has been investigated. The approach started with the regioselective BOC protection of commercially available norspermidine, spermidine and spermine plus the total synthesis of protected polyamines e.g. homospermidine and spermine. The nitrogen mustards chlorambucil and melphalan were conjugated to the polyamines at primary and secondary nitrogens via a variable length amide linkage to give a structural range of differentially charged polyamine-drug conjugates. The spin label 3-carboxy-proxyl was conjugated to a primary and secondary nitrogen of spermine via an amide linkage to give two novel spermine-spin labelled adducts. Electron paramagnetic resonance spin exchange experiments in the presence of DNA gave an indication of translational motion of spermine on the DNA. The DNA cross-linking of the polyamine-nitrogen mustards identified that: (i) spacing between positive charges does not significantly affect the cross-linking efficiency, (ii) increasing the positive charge of the polyamine increases the cross-linking ability of the conjugates (reflecting the trend in binding ability of charged polyamines) and (iii) primary amino polyamine-drug conjugates are more efficient cross-linkers than the corresponding secondary amino conjugates. The polyamine-nitrogen mustard conjugates also showed the same sequence selectivity as the parent drugs i.e. chlorambucil and melphalan. The N7 position in the major groove of DNA is alkylated. Runs of contiguous guanines provide sites of highest alkylation for chlorambucil and the polyamine-drug conjugates. The results imply that the initial site of alkylation is not dictated by the poly amine moiety binding to specific sites on DNA.
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Ogden, Dorothy. « Modifiable Hyperbranched Polyester Drug Delivery Systems ». Wright State University / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=wright1316178520.
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Fei, Dan. « Biodegradable polyanhydrides as drug delivery systems ». Thesis, Aston University, 2003. http://publications.aston.ac.uk/10949/.
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Polyanhydrides are useful biodegradable vehicles for controlled drug delivery. In aqueous media the breaking of the anhydride bonds resulting in gradually polymer fragments collapse and release drugs in a controlled manner. In this study, two new biodegradable polyanhydrides copolymers were synthesised using a melt-polycondensation method. The first is poly (bis (p-carboxyphenoxy)-2-butene-co-sebacic acid) (CP2B: SA), which has double bonds along the polymer backbone. The second is crosslinked poly (glutamic acid-sebacic acid-co-sebacic acid) (GluSA: SA), where the conjugated unit of glutamic acid with sebacic acid (glutamic acid-SA) acted as a crosslinking fragment in producing the crosslinking polymer. The two polymers were applied to preparation of microspheres with bovine serum albumin (BSA) as a model protein, using both double emulsion solvent evaporation and spray drying methods. The characterisation of the microspheres, morphology, particle size, and drug loading, was studied. The in vitro hydrolytic degradation of polymers and blank microspheres was monitored using IR, GPC, and DSC. In vitro drug release behaviour was also studied. Though the studies showed cleavages of anhydride bonds occurred rapidly (<5 days), bulks of the polymer microspheres could be observed after a few weeks to a month; and only around 10-35% of the protein was detectable in a four-week period in vitro. We found the pH of the medium exerts a large impact on the release of the protein from the microspheres. The higher the pH, the faster the release. Therefore the release of the protein from the polyanhydride microspheres was pH-sensitive due mainly to the dissolution of monomers from the microspheres.
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Liu, Weipeng. « Biopolymer-based ocular drug delivery systems ». Diss., Connect to online resource - MSU authorized users, 2008.
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Sodunke, Oluyomi. « Polymeric Micellar Network Derived from the Polymerization of Bicontiuous Microemulsion for Oral Drug Delivery Application ». University of Akron / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=akron1429738431.
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Chopra, Poonam. « Ocular Iontophoresis of Nanocarriers for Sustained Drug Delivery to the Eye ». University of Cincinnati / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1353951512.
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Cervantes, Martínez Claudia Violeta. « Porous and hybrid silica from biocompatible systems : application to drug release ». Electronic Thesis or Diss., Université de Lorraine, 2019. http://www.theses.fr/2019LORR0295.
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L'objectif de ce travail se concentre sur la préparation de matériaux poreux silicatés hybrides et dopés avec un principe actif, à base de composants biocompatibles pour des applications pharmaceutiques, en tant que systèmes d’administration de médicaments. La motivation de cette étude est liée à la nécessité de répondre à la demande croissante de médicaments plus efficaces. Le premier point d'intérêt de cette étude concerne les composés utilisés qui sont biocompatibles, peu coûteux, et qui, sont de bons candidats pour la formation de matériaux mésostructurés. Le tensioactif utilisé était le Kolliphor EL (KEL) et les huiles retenues étaient le Miglyol 812N (Mig), et le Myristate d’Isopropyl (IM). Le principe actif le Kétoprofène (KTP) a été choisi comme molécule modèle pour l’évaluation de les essaies de libération. En fin, les cellules HeLa, un type particulier de cellules cancéreuses, ont été utilisées pour évaluer la toxicité des matériaux synthétisés. Le premier chapitre est consacré à l'état de l'art des structures moléculaires à partir des tensioactifs non-ioniques, en particulière le KEL. Ensuite, les principales publications relatives aux matériaux poreux et hybrides en tant que vecteurs de drogues sont résumées. À la fin de ce chapitre, les modèles cinétiques de libération et les équations correspondantes sont présentées. Le second chapitre rassemble les modes opératoires et les techniques de caractérisation utilisés Le troisième chapitre étude le comportement de phase du système binaire KEL/eau étudié dans le cadre de ce travail est décrit. Les différents domaines à 1 et 2 phases ont été déterminés et caractérisés par inspection visuel, à l’aide de la microscopie optique à lumière polarisée et les structures aux des cristaux liquides par SAXS. Ensuite, l'influence de l'addition d’huile dans le système KEL/eau a été étudié à 25 °C Les diagrammes de phase ternaire ont été établis avec Miglyol (Mig) et Isopropyl Myristate (IM). À partir de ces systèmes à base de Mig et IM, des matériaux mésoporeux ont été préparés. Avec des conditions de synthèse optimisées, on a réussi à structurer le réseau mésoporeux dans les deux cas. Dans le quatrième chapitre l’influence de l’addition d’un copolymère block, le P123 dans le système KEL/eau est reportée et le diagramme de phase est présente. Il a permis d'évaluer la synergie des deux tensioactifs pour former des micelles et des cristaux liquides. Ensuite, l’effet de l’addition de micelles de P123 dans les émulsions fines á base d’Isopropyl Myristate sur les caractéristiques des matériaux poreux ainsi préparés en utilisant différentes teneurs de micelles de P123, il est possible de faire varier le degré de porosité des matériaux. Pour des proportions émulsions (Em)/micelles P123 inférieures à 50/50, on obtient des silices mésoporeuses avec deux tailles de pores. Lorsque le rapport Em/P123 augmente, est possible de contrôler la porosité des matériaux. Le cinquième chapitre concerne sur l'étude de l'encapsulation de KTP dans différents systèmes et de sa libération. Des émulsions concentrées ainsi que des matériaux hybrides à base de solutions micellaires et d'émulsions fines ont été sélectionnés. Les études de libération ont été effectuées avec une solution de PbS a différents pH :7,4; 1,2 et 4,6. Les résultats ont montré que, dans des conditions neutres, le KTP libéré par les matériaux hybrides à base des solutions micellaires atteint 38% au bout de 24h et l’effet du pH permet d’augmenter la quantité de KTP libéré. Ensuite, la libération dans une solution réceptrice avec diffèrent concentrations de P123 a été étudié. Les résultats montrent que la quantité de KTP libéré en présence de 5% de P123, atteindre 65% au bout de 24h. Dans la dernière partie, la toxicité des matériaux et des systèmes hybrides dopés a été évalué. Les résultats montrent que la matrice de silice protège les cellules car la viabilité cellulaire est augmentée, de 64 à presque 80% avec les matériaux hybridesThe objective of this work focuses on the preparation of porous, hybrid silicate materials doped with an active ingredient, based on biocompatible components for pharmaceutical applications, as drug delivery systems. The motivation for this study is related to the need to meet the growing demand for more effective drugs. The first point of interest of this study concerns the compounds used which are biocompatible, low-cost, and which are good candidates for the formation of mesostructured materials. The surfactant used was Kolliphor EL (KEL) and the oils were Miglyol 812N (Mig), and Isopropyl Myristate (IM). The active ingredient Ketoprofen (KTP) was chosen as the molecule model for the evaluation of release assays. Finally, HeLa cells, a cancer cell, were used to assess the toxicity of the synthesized materials. The first chapter is devoted to the state of the art of molecular structures based on non-ionic surfactants as KEL. Then, the main publications relating to porous and hybrid materials as drug carriers are summarized. At the end of this chapter, the kinetic release models and corresponding equations are presented. The second chapter brings together the methods and characterization techniques used. The third chapter studies the phase behaviour of the KEL/water binary system studied in this work and is described. The different 1- and 2-phase domains were determined and characterized by visual inspection, using polarized light optical microscopy and liquid crystal structures by SAXS. Then, the influence of oil addition in the KEL/water system was studied at 25°C. Ternary phase diagrams were established with Miglyol (Mig) and Isopropyl Myristate (IM). From these Mig and IM-based systems, mesoporous materials were prepared. With optimized synthesis conditions, the mesoporous network was structured in both cases. In the fourth chapter the influence of the addition of a block copolymer, the P123 in the KEL/water system is reported and the phase diagram is present. It evaluated the synergy of the two surfactants to form micelles and liquid crystals. Then, the effect of the addition of P123 micelles in Isopropyl Myristate based fine emulsions on the characteristics of the porous materials thus prepared using different P123 micelle contents, it is possible to vary the degree of porosity of the materials. For emulsion (Em)/micelle P123 proportions less than 50/50, mesoporous silicas with two pore sizes are obtained. When the Em/P123 ratio increases, it is possible to control the porosity of the materials. The fifth chapter concerns the study of the encapsulation of KTP in different systems and its release. Concentrated emulsions as well as hybrid materials based on micellar solutions and fine emulsions have been selected. Release studies were performed with a PbS solution at different pH levels: 7.4; 1.2 and 4.6. The results showed that, under neutral conditions, the KTP released by hybrid materials based on micellar solutions reaches 38% after 24 hours and the pH effect increases the amount of KTP released. Then, the release into a receptor solution with different concentrations of P123 was studied. The results show that the amount of KTP released in the presence of 5% P123, reach 65% after 24 hours. In the last part, the toxicity of doped materials and hybrid systems was assessed. The results show that the silica matrix protects the cells because cell viability is increased, from 64 to almost 80% with hybrid materials
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Jørgensen, Lene. « Lipid based drug delivery systems for parenteral delivery of proteins / ». Cph. : Department of Pharmaceutics, the Danish University of Pharmaceutical Sciences, 2004. http://www.dfh.dk/phd/defences/lenejoergensen.htm.
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Zhang, Ling Centre for Advanced Macromolecular Design Faculty of Engineering UNSW. « Well defined stimuli-responsive cross-linked micelles as biocompatible drug/gene delivery system from RAFT polymerization ». Publisher:University of New South Wales. Centre for Advanced Macromolecular Design, 2009. http://handle.unsw.edu.au/1959.4/43362.
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The objective of this thesis is to investigate well-defined cross-linked particles synthesized via the reversible addition fragmentation chain transfer (RAFT) process that can be used for drug delivery. To achieve this aim, a wide range of cross-linked micelle systems have been synthesized and intensively investigated. Various biocompatible monomers were employed, including poly (ethylene glycol) methyl ether methacrylate, 2-hydroxyl ethyl acrylate, functionalized glucosamine and nucleotides containing monomers. Different cross-linked structures were used, for example, core-cross-linked, nexus-cross-linked and shell-cross-linked micelles. Diverse stimuli-responsive particles were used, such as pH-sensitive, thermo-sensitive and thiol-sensitive cross-linked systems. Evidences of the successful synthesis of all the resulting cross-linked products are given. They displayed better properties, as drug carriers, than non-cross-linked micelles. A thermo-responsive seven-arm star glycopolymer, synthesized via the RAFT process, was also investigated.
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Song, Lin. « STUDIES OF SOLUBILIZATION OF POORLY WATER-SOLUBLE DRUGS DURING IN VITRO LIPOLYSIS OF A MODEL LIPID-BASED DRUG DELIVERY SYSTEM AND IN MIXED MICELLES ». UKnowledge, 2011. http://uknowledge.uky.edu/pharmacy_etds/1.
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Lipid-based drug delivery systems (LBDDSs) are becoming an increasingly popular approach to improve the oral absorption of poorly-water soluble drugs. Several possible mechanisms have been proposed to explain the means by which LBDDSs act in vivo to enhance absorption. The goal of the current dissertation is to provide a better understanding of one proposed mechanism; the capability of lipoidal components in LBDDS formulations to create and maintain a drug in a supersaturated state under simulated GI conditions. Moreover, molecular details of equilibrium solubilization of a drug in a series of model lipid assemblies were examined. The results of these studies will aid formulators in choosing the optimal LBDDS to improve oral absorption of poorly water-soluble drugs.
Time-dependent solubilization behavior of progesterone, 17β-estradiol and nifedipine in a simple model LBDDS composed of Polysorbate 80 was assessed employing the in vitro dynamic lipolysis model. The results illustrated the extent to which the supersaturated state was dependent on the extent of lipolysis of Polysorbate 80 and the initial drug concentration. Area-under-the curve-supersaturation was proposed as a means of quantifying the time-dependent extent of supersaturation in LBDDSs in simulated intestinal conditions.
Concurrently, a series of model mixed micellar solutions, composed of Polysorbate 80 and oleic acid, were prepared to represent the lipid assemblies produced during the lipolysis experiments. The ability of these aggregates to solubilize progesterone, 17β-estradiol and nifedipine were evaluated and the aggregate/water partition coefficients were determined. The Treinor model was found to successfully fit the partition coefficients of the drugs in a range of mixed micelles. The equilibrium solubility of drugs in the mixed micelles was calculated and compared to that found under lipolytic conditions. The best agreement between calculated and experimental conditions was observed for nifedipine. These studies have established a foundation for the evaluation of time-dependent extent of supersaturation with more complex LBDDS formulations exposed to lipolytic conditions.
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Baki, Mert. « Bone Marrow Targeted Liposomal Drug Delivery Systems ». Master's thesis, METU, 2011. http://etd.lib.metu.edu.tr/upload/12613251/index.pdf.
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Homing is the process that stem cells move to their own stem cell niches under the influence of chemokines like stromal-derived factor-1&alpha(SDF-1&alpha
) upon bone marrow transplantation (BMT). There is a need for increasing homing efficiency after BMT since only 10-15% of the transplanted cells can home to their own niches and a limited amount of donor marrow can be transplanted. In this study, we aimed to develop and characterize bone marrow targeted liposomal SDF-1&alpha
delivery system prepared by extrusion method. Alendronate conjugation was chosen to target the liposomes to bone marrow microenvironment, particularly the endosteal niche. Optimization studies were conducted with the model protein (
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Zaid, Alkilani Ahlam. « Polymeric microneedle systems for transdermal drug delivery ». Thesis, Queen's University Belfast, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.603301.
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Delivery across skin offers many advantages compared to oral or parenteral routes e.g. non-invasive, avoiding first-past metabolism, improved bioavailability and reduction of systemic side effects. Microneedle (MN) are minimally-invasive devices that painlessly by-pass the skin's stratum corneum, which is the principal barrier to topically-applied drugs. Polymeric MN delivery systems were designed and evaluated to transdermally deliver two model drugs, the small water soluble drug ibuprofen sodium and the large protein ovalbumin (OVA). A range of hydrogel forming materials for MN production was evaluated to identify the most suitable super swelling hydrogel MN array that are hard in the dry state but, upon insertion into skin, rapidly take up interstitial fluid. The MN themselves contain no drug, but instead drug are loaded into lyophilized patches. Novel super swelling hydrogel forming MN arrays were fabricated from aqueous blends containing 20% w/w poly(methyl vinyl ether co maleic acid) (Gantrez® S97), 7.5% w/w poly(ethylene glycol) (PEG) and 3% sodium carbonate (Na2C03). In addition, dissolving MN arrays loaded with a high dose of non-potent therapeutic drug were fabricated from aqueous blends of 70% w/w Gantrez® AN139 (PH 7) and 30% ibuprofen sodium. Successful drug delivery was achieved in this research work using novel polymeric MN, super swelling hydrogel MN and dissolving MN. The in vitro studies has been shown first ever example of polymeric MN being loaded with a NSAIDs. The novel concept of super swelling hydrogel MN integrated with lyophilized patches loaded with ovalbumin was evaluated. They enabled the sustained delivery of the ibuprofen sodium and ovalbumin both in vitro and in vivo. Gamma sterilization can be done without compromising polymeric MN properties. Finally, hydrogel forming MN arrays can be successfully and reproducibly applied by human volunteers given appropriate instruction so the use of MN applicator devices may not be necessary, thus possibly enhancing patient compliance.
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Lawlor, Michelle S. « Rheological characterisation of bioadhesive drug delivery systems ». Thesis, Queen's University Belfast, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326370.
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Berwick, James Miles. « Surface-engineered biomimetic systems for drug delivery ». Thesis, University of Nottingham, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.416292.
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Zhang, Huizhen. « Liposome drug delivery systems for anticancer agents ». Scholarly Commons, 2008. https://scholarlycommons.pacific.edu/uop_etds/711.
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Development of liposome formulation of an amphiphilic anticancer peptide using the ANTS/DPX leakage assay. The effects of lipid composition on the liposomes' resistance to an amphiphilic cyclic peptide c[KS.S.S.KWL W] were studied by the ANTS/DPX leakage assay. One or more unsaturated acyl chains in the phospholipids, small phospholipid headgroup size, the presence of cholesterol, and the presence of PEG-lipid were demonstrated as critical parameters to stabilize the liposome membrane. A liposome formulation of the peptide comprising POPE/POPC/cholesterol/C16 mPEG 2000 ceramide (20.8:31.2:40:8, mol%) was thereby developed with a peptide-encapsulation efficiency of 47.8%. The liposomal cyclic peptide exhibited dose-dependent toxicity to MCF7 human breast cancer cells and stability under incubation.
Design, construction and in vitro characterization of a hydrazone-based convertible liposomal system for anticancer drug delivery. A novel PEG-lipid, PEG2ooo-Hz-DHG, with an acid-labile hydrazone linker between the PEG2ooo head group and the lipidic DHG moiety was synthesized. PEG2000-Hz-DHG was relatively stable at normal physiological pH 7.4, but hydrolyzed more quickly at tumor interstitium pH 6.5-7.0 and endosomal/lysosomal pH 5.0. A novel pH-sensitive "Convertible Liposome System" (CLS) was constructed comprising PEG2ooo-Hz-DHG, positively charged lipid DOTAP, and the zwitterionic phospholipid POPC (8:15:77, mol%). CLS converted from neutrally charged "stealth" liposome to positively charged liposome at tumor interstitual pH owing to the hydrolysis ofPEG2ooo-Hz-DHG. The doxorubicin-encapsulated CLS that had been pre-incubated at pH 6.5 for 30 h exhibited more intensive binding and higher toxicity to Bl6-Fl0 murine melanoma and MDA-MB-435S human breast cancer cells than doxorubicin encapsulated in pH-insensitive stealth liposome.
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McMillan, Hannah Louise. « Sustained release biodegradable ocular drug delivery systems ». Thesis, Queen's University Belfast, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.678216.
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Delivery of drugs to the posterior segment of the eye is notoriously difficult and unfortunately many chronic conditions of the posterior segment often lead to sight-loss if not treated effectively. Current methods of delivery such as topical drops result in poor bioavailability at the back of the eye, while the blood brain retina imposes restrictions on the entry on drugs into the eye delivered by the systemic system. The gold-standard method for delivery of therapeutic concentrations of drugs is intravitreal delivery, which involves an injection into the vitreous cavity. Although this provides therapeutic levels of drugs, numerous injections are required to maintain these concentrations, and the frequency of injection can cause various adverse effects such as retinal detachment, vitreous haemorrhage and endophthalmitis. The present study investigates the potential use of solvent-induced in situ forming implants (ISFI) as a method of delivering drugs in a prolonged manner to the posterior segment of the eye. These systems are composed of a water-insoluble polymer dissolved in an organic solvent. Their low viscosity allows for easy administration through small-bore needles (e.g. 27 gauge) and on contact with an aqueous environment, such as the vitreous humour, phase inversion through solvent exchange takes place resulting in a biodegradable polymeric implant that can release drugs for an extended period. . As another method to improve posterior drug delivery in a minimally-invasive manner, microneedles (MN) were used to inject small amounts of ISFI formulation into sclera. Drug release and permeation stUdies across sclera indicated that the use of MN did indeed improve scleral permeation, with potential to allow posterior drug delivery from an intrascleral depot. From investigations carried out in the present study, ISFI show promise in transforming drug delivery to the eye and therefore possibly preventing the loss of sight in numerous individuals.
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He, Xingyu. « Long-term Light-activated Drug Delivery Systems ». University of Cincinnati / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1613752062550859.
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Huang, Tien-Lu. « Oscillating Aqueous Gels as Drug Delivery Systems ». The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1366066532.
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Yung, Bryant Chinung. « NANOPARTICLE DRUG DELIVERY SYSTEMS FOR CANCER THERAPY ». The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1417614665.
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Senderoff, Richard I. « Development of fibrin-based drug delivery systems / ». The Ohio State University, 1990. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487677267728699.
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Apps, MIchael Garry. « Platinum anticancer drugs and drug delivery systems ». Thesis, The University of Sydney, 2015. http://hdl.handle.net/2123/14409.
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In this thesis two different ways to improve platinum-based chemotherapy were investigated. The first was through the use of a new slow release clay-based drug delivery vehicle and the second through the design and synthesis of novel dinuclear platinum complexes. For the clay-based drug delivery research, the platinum anticancer complex [(1,10-phenanthroline)(1S,2S-diaminocyclohexane)platinum(II)] chloride, PHENSS, was loaded into montmorillonite (MMT) clay. The PHENSS was found to be incompletely burst released from the MMT. The MMT also had a negative effect on the in vitro cytotoxicity of PHENSS in the human breast cancer cell lines MCF-7 and MDA-MB-231. Overall the results demonstrate that MMT is not a suitable slow release vehicle for PHENSS. For the dinuclear platinum complex synthesis research, new bispyridine-based bridging ligands were synthesised using an amide coupling reaction. The bridging ligands were then reacted with transplatin to yield the dinuclear platinum complexes. The platinum complexes have potential application as anticancer agents and the synthetic method can be modified to produce other multinuclear complexes.
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Chia, Leonard Sze Onn. « Investigating controlled release pulmonary drug delivery systems ». Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/273209.
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The therapeutic effect of pulmonary drug delivery systems is limited by its rapid clearance from the lungs by robust clearance mechanisms. By controlling the release of drugs, the therapeutic effect of pulmonary drug delivery systems, as well as patient convenience and compliance could be improved by reducing the number of times drugs need to be administered. In this study, two controlled pulmonary drug delivery systems for drugs of different solubilities were investigated and they were characterised for their viability as effective controlled release pulmonary drug delivery systems, particularly in areas of aerosol performance and dissolution profile. A hybrid protein-polymer controlled release pulmonary drug delivery system was developed to sustain the release of a water-soluble anti-asthma drug, cromolyn sodium (CS). Two excipients with complementary characteristics – a protein, bovine serum albumin, and a polymer, polyvinyl alcohol – were formulated together with CS via co-spray drying, with varying protein-polymer ratios and drug loadings. The hybrid particles showed promise in combining the positive attributes of each excipient, with respirable particles shown to sustain the release of CS with a fine particle fraction of 30%. Combining the two excipients was complex, with further optimisation of the hybrid formulations possible. A commercially available polymer, Soluplus® was spray-dried with a poorly-water soluble corticosteroid, beclomethasone dipropionate (BDP). The resultant respirable powders were shown to have potential for use as a controlled release pulmonary drug delivery system with up to 7-fold improvement in the amount of BDP released compared to spray-dried BDP. The spray-dried BDP-Soluplus® powders were found to be amorphous, and physically stable against re-crystallisation for up to 9 months at accelerated stress test conditions with drug loadings of up to 15 % (w/w). Although it provided a platform to compare between formulations, the USP 4 flow-through cell dissolution apparatus was found to be inadequate to accurately study the dissolution profiles of the pulmonary drug delivery systems due to the formation of a gel in the apparatus. Preliminary work on the use of a novel technique to predict the crystallisation of amorphous formulations with terahertz time-domain spectroscopy was also conducted. The system confirmed the re-crystallisation tendencies of several hybrid CS/BSA/PVA formulations. Modification to the experimental setup to probe the formulations at different relative humidities instead of temperatures could yield improved results.
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Giglio, Valentina. « Biofunctionalized systems for drug discovery and delivery ». Doctoral thesis, Università di Catania, 2016. http://hdl.handle.net/10761/3893.
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During this doctoral research work new potential drug delivery vehicles for targeted treatment of cancers were developed. For this purpose, both soft and hard materials were subject of study.
Firstly, the synthesis, the characterization and the biological evaluation of monomeric â-cyclodextrins functionalized with folic acid (FA) were the focus of this research. In particular, four new conjugates (CyD-FAs), both 3- and 6-functionalized â-CyDs (â-CyD3 and â-CyD6) linked to the á- or ã-carboxylic group of the FA were synthesized, isolated and fully characterized. Furthermore, the ability of these compounds to include the anticancer drug LA-12 and to deliver it selectively to FR (+) tumor cell lines was investigated.
Since the promising results obtained with these CyD-FA conjugates as carriers for LA-12, polymeric nanoparticles based on cross-linked cyclodextrins were designed for drug delivery purposes. These systems, offer the advantages of CyD-type complexation in a synergistic way, resulting more effective than the parent CyDs. In particular, CyD-based polymers and oligomers were synthesized, functionalized with FA and tested as delivery systems towards different hydrophobic anticancer or anti-inflammatory agents. Furthermore, for selected systems, the binding constants of the formed inclusion complexes were determined as well.
Concerning hard materials, mesoporous silica nanoparticles were investigated. A new disc-shaped mesoporous material, the nanodiscs (NDs), was synthesized, isolated and fully characterized. This material was firstly used for the preparation of self-assembled monolayers (SAM), to be employed in targeted cancer cell adhesion and in-situ drug delivery. For this purpose, the NDs-monolayers were functionalized with FA as targeting moiety. Thanks to their large surface area and the possibility of high density of superficial functionalization with bioactive molecules, these systems resulted effective in binding cancer cells even upon short contact times. Moreover, exploiting the porosity of the synthesized particles, the intracellular release of small hydrophobic molecules pre-loaded in the channels of the NDs were achieved.
Secondly, preliminary biological experiments carried out to test the cellular uptake of NDs, and the drug-carrier ability were performed. Finally, in the attempt to increase the biodegradability of these interesting structures, disulfide-doped mesoporous silica nanodiscs (ss-NDs) were also prepared. Full characterization and preliminary biological assays of these hybrid materials was also performed, and their degradation in redox conditions investigated. This novel material, taking advantage of bio-redox reactions, undergoes a controlled disintegration process in presence of reducing agents (i.e. glutathione), displaying an improved drug delivery action.
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Al-Kassas, Raida. « Design of particulate delivery systems ». Thesis, Queen's University Belfast, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.239000.
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Zderic, Vesna. « Ultrasound-enhanced ocular drug delivery / ». Thesis, Connect to this title online ; UW restricted, 2004. http://hdl.handle.net/1773/8085.
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Lungare, Shital. « Development of novel delivery systems for nose-to-brain drug delivery ». Thesis, Aston University, 2017. http://publications.aston.ac.uk/37491/.
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The blood brain barrier (BBB) poses a significant hurdle to brain drug delivery. However, the location of the olfactory mucosa, within the nasal cavity, is a viable target site for direct nose-to-brain (N2B) delivery, thereby bypassing the BBB. To exploit this target site innovative nasal formulations are required for targeting and increasing residency within the olfactory mucosa. We developed and characterised three formulation systems for N2B delivery, (i) thermoresponsive mucoadhesion nasal gels sprays; (ii) mesoporous silica nanoparticles and (iii) nasal pMDI devices. We developed an optimal mucoadhesive formulation system incorporating amantadine as a model, water-soluble anti-Parkinson’s drug using carboxymethy cellulose and chitosan as mucoadhesives. Formulations demonstrated droplet sizes of < 130mm and stability over 8-weeks when stored at refrigeration conditions with no significant cellular toxicity against olfactory bulb (OBGF400) and nasal epithelial (RPMI 2650) cells. Mesoporous silica nanoparticles (MSNP) were prepared (~220nm) and demonstrated cellular uptake into OBGF400 within 2-hours of incubation with minimal toxicity. MSNP were loaded with two novel phytochemicals known to possess CNS activity, curcumin and chrysin, with loading efficiencies of ~12% confirmed through TGA, DSC and HPLC-UV analysis. Furthermore, a pH dependant release profile was identified with curcumin with greater release at nasal cavity pH 5.5 compared to pH 7.4. Furthermore, successful incorporation of MSNP into nasal gels was demonstrated through rheological studies with a decrease in Tsol-gel. A pilot study was conducted to assess the feasibility of modified existing pulmonary pMDI to deliver diazepam intranasally, targeting the olfactory mucosa. Diazepam was formulated with HFA134a and using ethanol as a co-solvent, and demonstrated stability in formulation over 3 months. Deposition studies within a nasal cast model demonstrated 5-6% deposition onto the olfactory mucosa under optimal administration conditions in the absence of any nozzle attachments. Our studies have provided a basis for the development to innovative intranasal formulation systems potentially capable of targeting the olfactory mucosa for both water soluble and poorly soluble drugs.
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Yang, Xiaojuan. « Development of Nanoparticle Systems for Therapeutic Drug Delivery ». The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1248972068.
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Park, Jung-Hwan. « Polymeric microneedles for transdermal drug delivery ». Diss., Available online, Georgia Institute of Technology, 2004:, 2004. http://etd.gatech.edu/theses/available/etd-06072004-131324/unrestricted/park%5Fjung-hwan%5F200405%5Fphd.pdf.
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