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Porter, Christopher John Hamilton. "Targeting collodial drug carriers to the bone marrow." Thesis, University of Nottingham, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.315061.
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Oidu, Benjamin. "Uptake of liposomes into bacterial cells." Thesis, Nelson Mandela Metropolitan University, 2013. http://hdl.handle.net/10948/d1021010.
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Liposomes are small phospholipid vesicles that have been widely investigated as drug carriers for the delivery of therapeutic agents. A variety of liposome formulations are presently under clinical trial exploration, while others have already been approved for clinical use. The aim of this study was to optimize liposome uptake into bacterial cells. Both gram-positive and gram-negative bacteria were used in the study as well as Candida albicans.Response surface methodology (RSM) using a central composite design (CCD) model was used to optimize liposomal formulations of carboxyfluorescien (CF) for each of the three microbes, and also the three microbes in combination namely; Staphylococcus aureus (Sa), Escherichia coli (Ec) and Candida albicans (Ca). Percentage of CF encapsulated and CF increase in Uptake were investigated with respect to two independent variables that were, cholesterol (CHOL) and stearylamine (SA) content. Design Expert 8 was used for the purpose of finding the combination of independent variables that would yield an optimal formulation for each microbe and the three microbes in combination. The model selected by the software managed to reasonably correlate the predicted models to the experimental data. Encapsulation of carboxyfluorescien (CF) into a liposome formulation enhanced its uptake by Staphylococcus aureus and Escherichia coli as well as Candida albicans. This was evident in the increase in CF uptake when the uptake rate of free CF was compared with that of liposomal CF.
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Miknevičiūtė, Kristina. "Interactions of biodegradable drug carriers with hydrophilic medium." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2007. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2007~D_20070802.101122-62998.
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The aim of this thesis “Interactions of biodegradable drug carriers with hydrophilic medium” is the study of polymer-hydrophilic medium interactions from the point of view of swelling, erosion and glass transition. In the theoretical part attention was paid to basic information about polyester amides and polyesters with molecule linear, branched, and chain extended. In this part, some basic relations were used, concerning various aspects of biodegradation of polymers, thermal analysis of amorphous phase of polymers and pharmaceutical particulate systems. The main part of the thesis is focused on experiment. Fifteen recently synthesized oligomeric and polymeric carriers were studied in the aspect of their swelling and erosion course. Some of these oligoesters with molecular linear constitution were evaluated during in vitro degradation process via glass transition tested by DSC method measurements. No correlation signs between swelling kinetics and glass transition temperature values course were found. These two molecular relaxation parameters are the manifestations of different mechanism. Swelling extent is influenced by osmotic phenomena, whilst glass transitions by molecule polarization effects. This work is one of the first steps examining these drug carriers. The results of this work will be used in choosing perspective drug carriers and in further researches.Šio darbo „Biodegraduojančių vaistų nešėjų sąveika su hidrofiline terpe“ tikslas ištirti polimero bei hidrofilinės terpės sąveiką atsižvelgiant į brinkimą, eroziją bei stiklėjimo temperatūros pokyčius, galimą ryšį tarp polimero brinkimo ir stiklėjimo temperatūros, apžvelgti nano ir mikro dalelių paruošimo bei įvertinimo teoriją. Literatūros apžvalgoje dėmesys skiriamas informacijai apie poliesteramidus ir linijinius, šakotus ar praplėstos grandinės poliesterius. Šioje dalyje aptariami įvairūs polimerų biodegradacijos, amorfinės fazės polimerų terminės analizės aspektai, taip pat nano bei mikrodalelės kaip vaisto forma. Pagrindiniai darbo uždaviniai yra ištirti penkiolika neseniai susintetintų oligomerinių bei polimerinių vaistų nešėjų atsižvelgiant į jų brinkimą bei eroziją, įvertinti kai kurių linijinių oligoesterių degradacija in vitro atsižvelgiant į stiklėjimo temperatūrą matuojant diferencinės skenuojančios kalorimetrijos metodu. Atkreiptas dėmesys į galimą ryšį tarp stiklėjimo temperatūros ir brinkimo kinetikos, kurio nepastebėta; manoma, kad dėl to, jog molekulės grandinės atsipalaidavimas pasireiškia dėl skirtingų mechanizmų. Brinkimo laipsnis priklauso nuo osmotinių reiškinių, o stiklėjimo temperatūrai įtaką daro molekulės poliarizacija. Šis darbas yra pradinis etapas tiriant šiuos polimerus. Šio darbo rezultatai padės atrenkant perspektyvias medžiagas tolimesniems tyrimams, prognozuojant galimas jų panaudojimo galimybes.
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Corswant, Christian von. "Lecithin-based microemulsions for pharmaceutical use phase behavior and solution structure /." Lund : Lund University, 1998. http://catalog.hathitrust.org/api/volumes/oclc/68945035.html.
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Azevedo, Eduardo Pereira de. "Aldehyde-functionalized chitosan and cellulose:chitosan composites: application as drug carriers and vascular bypass grafts." Diss., University of Iowa, 2011. https://ir.uiowa.edu/etd/1119.
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In this work, aldehyde-functionalized chitosan was produced by the reaction of chitosan in the solid state with nitrogen oxide gases, generated in situ from a HNO3/H3PO4 - NaNO2 mixture. This reaction is more advantageous than the existing methods to produce aldehyde-functionalized chitosan, since the depolymerization was slower and the purification process of the products was easy and straightforward. The appearance of characteristic peaks in the Fourier transform infrared and carbon-13 nuclear magnetic resonance spectra (1733 cm-1 and 183.4 ppm, respectively) of the product confirms the presence of the aldehyde functionality in the modified chitosans. The pH-dependent 1H-NMR spectra also revealed the presence of aldehyde groups. However, as the pH increased from 2.0 to 6.0, the resonance due to the aldehyde gradually disappeared and a new resonance appeared at 8.05 ppm, which is attributable to the formation of Schiff's base between the aldehyde and the free amine groups. This aldehyde-derivative of chitosan formed a gel in situ by simply dissolving it in water at a concentration of 6% (w/w) without any added external crosslinker. This gel show potential use as drug carrier and as scaffold for vascular tissue engineering.
In addition, cellulose:chitosan composites were prepared with the main purpose of obtaining a compliant hollow tube for vascular bypass application. Elastic properties of membranes made of this composite with different ratios between each polymer were determined using uniaxial tests and the ratio that yielded the less stiff membrane was chosen to prepare a small diameter hollow tube. The presence of chitosan had a favorable impact on the elasticity of the membranes, where the cellulose:chitosan 5:5 ratio showed the lowest Young's modulus. Small diameter tubular constructs were fabricated using this optimal cellulose:chitosan ratio and assessed for their suitability as coronary artery bypass grafts. The compliance of the tubes was found to be 5.91 %/mmHg x 10-2, which is higher than those of Dacron, ePTFE and saphenous vein. Burst strength tests revealed that the tubes can withstand at least 300 mmHg. Finally, the tubes showed satisfactory cell attachment property when myofibroblast cells adhered and proliferated on the lumen of the samples.
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Man, Kwun-wai Dede, and 文冠慧. "Oleanolic acid delivery using biodegradable nanoparticles for cancer therapy." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2015. http://hdl.handle.net/10722/208550.
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Lendemans, Dirk G., and n/a. "Novel cationic preparations of iscoms as vaccine carriers." University of Otago. School of Pharmacy, 2006. http://adt.otago.ac.nz./public/adt-NZDU20060810.141916.
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Aim of thesis: Immuno-stimulating complexes (ISCOMs) are particulate vaccine delivery systems composed of Quillaja saponins, cholesterol and phospholipid. ISCOMs are typically spherical cage-like structures with a diameter of 40 nm and carry a negative charge. Incorporation of the respective vaccine antigen into the particles generates more potent vaccines than a simple mixture of both vaccine components. This requires the antigen to display either hydrophobic domains or positive charges, which allow interaction with the ISCOM particles. However, not all antigens fulfil this requirement and modification of these becomes necessary. Hence, the aim of this study was to design novel preparations of ISCOMs with a positive charge, suitable for adsorption of native hydrophilic antigens and poly-nucleotides, and test their potential as a novel vaccine carrier platform.
Methods: Two cationic lipids, DC-cholesterol and DOTAP, were selected to prepare the cationic modifications of ISCOMs. DC-cholesterol substituted for cholesterol in classical ISCOMs, whereas DOTAP substituted for their phospholipid component. The phase behaviour of colloidal systems containing Quil-A, phosphatidylcholine (PC) and DC-cholesterol and of colloidal systems comprised of Quil-A, cholesterol and DOTAP was studied by transmission electron microscopy (TEM). Lipid-film hydration was utilised as the first method to prepare these colloidal systems. Selected compositions containing either DC-cholesterol or DOTAP were also prepared by dialysis as second method. A novel third method for preparing homogenous dispersions of classical ISCOMs was developed utilising ethanol injection. This method was also applied in an attempt to prepare cationic modifications of ISCOMs including DC-cholesterol and DOTAP. As in the colloidal systems comprising Quil-A, PC and DC-cholesterol transformations of structures were observed upon dilution with aqueous solutions, these transitions were also studied on classical ISCOMs using TEM and dynamic light scattering techniques. Loading of cationic colloidal structures composed of Quil-A, PC and DC-cholesterol was performed with the model protein antigen ovalbumin (OVA) and a model plasmid, and the resulting structures were analysed by fluorescence spectroscopy, TEM and gel electrophoresis. The immunological properties of non-loaded and OVA-loaded structures were studied in terms of their ability to activate murine bone marrow derived dendritic cells (mBMDC) as antigen presenting cells (APC) and OVA-specific CD8+ T cells in vitro.
Results: Substitution of cholesterol in classical ISCOMs with DC-cholesterol resulted in the formation of cationic cage-like structures similar to the classical particles. These were observed in pseudo-ternary Quil-A:PC:DC-cholesterol systems and even in pseudo-binary Quil-A:DC-cholesterol systems prepared by lipid-film hydration. Compositions at which cage-like structures were observed included high weight proportions of DC-cholesterol (> 60%). However, samples were relatively heterogeneous, and aggregation of colloidal structures was observed at equimolar ratios of Quil-A and DC-cholesterol. The ionic strength, pH and composition of the hydration buffer were demonstrated to be important variables influencing the formation of cage-like structures. Morphological changes of pre-formed cationic cage-like structures were observed upon dilution. However, classical anionic ISCOMs showed a similar behaviour. The numbers of cationic cage-like structures appeared to increase upon prolonged storage of samples. Purification of structures and longitudinal analysis of their composition suggested an increased formation of stoichiometrically defined DC-cholesterol:Quil-A:PC complexes over time, rather than a change in composition. The substitution of phospholipid in classical ISCOMs with DOTAP also resulted in heterogeneous dispersions, and aggregation of colloidal structures was observed at equimolar ratios of Quil-A and DOTAP. Phase separation phenomena were proposed based on TEM observations. However, the formation of cage-like particles with a positive [zeta]-potential was not observed. Although ethanol injection was introduced as a novel method to prepare classical ISCOMs, its application did not result in more homogenous dispersions of cationic colloidal structures containing DC-cholesterol or DOTAP. Dialysis also failed to produce higher numbers of well-defined cationic particles, although using this method homogeneous, anionic ISCOM-like particles containing DOTAP were obtained. The efficient adsorption of OVA and plasmid DNA onto cationic structures containing Quil-A, PC and DC-cholesterol was demonstrated. The adsorption process was accompanied with a decrease in [zeta]-potential, aggregation of structures and changes in the ultra-structure, particularly at high protein:lipid ratios. The in vitro immunogenicity of dispersions containing Quil-A, PC and DC-cholesterol was equivalent to that of classical ISCOMs in terms of activation of mBMDC and OVA-specific CD8+ T cells, even though smaller amounts of Quillaja saponins and total lipid were co-delivered with OVA. Furthermore, the uptake of OVA by BMDC appeared to be more efficient in conjunction with the novel cationic dispersions.
Conclusions: Cationic colloidal structures containing Quillaja saponins offer great potential as vaccine delivery systems. Their advantages thus far include simple and efficient adsorption of antigen, efficient uptake by APC and immunological activity in vitro. With further development, cationic carriers containing Quillaja saponins may constitute a very potent vaccine delivery platform suitable for a variety of subunit antigens, and suffice both pharmaceutical and immunological requirements.
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Nadkarni, Sreekant Raghuveer. "Controlled delivery of pilocarpine." Diss., The University of Arizona, 1990. http://www.gbv.de/dms/bs/toc/128390700.pdf.
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Saraf, Poonam S. "RGD based peptide amphiphiles as drug carriers for cancer targeting." Scholarly Commons, 2014. https://scholarlycommons.pacific.edu/uop_etds/137.
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Specific interactions of ligands with receptors is one of the approaches for active targeting of anticancer drugs to cancer cells. Over expression of integrin receptors is a physiological manifestation in several cancers and is associated with cancer progression and metastasis, which makes it an attractive target for cancer chemotherapy. The peptide sequence for this integrin recognition is the Arg-Gly-Asp (RGD). Self-assembly offers a unique way of presenting ligands to target receptors for recognition and binding. This study focuses on development of integrin specific peptide amphiphile self-assemblies as carriers for targeted delivery of paclitaxel to α v β 3 integrin overexpressing cancers. Amphiphiles composed of conjugates of different analogs of RGD (linear, cyclic or glycosylated) and aliphatic fatty acid with or without 8-amino-3,6-dioxaoctanoic acid (ADA) as linker were synthesized and characterized. The amphiphiles exhibited Critical Micellar Concentration in the range of 7-30 μM. Transmission electron microscopy images revealed the formation of spherical micelles in the size range of 10-40 nm. Forster Resonance Energy Transfer studies revealed entrapment of hydrophobic dyes within a tight micellar core and provided information regarding the cargo exchange within micelles. The RGD micelles exhibited competitive binding with 55% displacement of a bound fluorescent probe by the cyclic RGD micelles. The internalization of fluorescein isothiocynate (FITC) loaded RGD micelles was significantly higher in A2058 melanoma cells compared to free FITC within 20 minutes of incubation at 37°C. The same micelles showed significantly lower internalization at 4°C and on pretreatment with 0.45M sucrose confirming endocytotic uptake of the RGD micellar carriers. The IC50 of paclitaxel in A2058 melanoma cells was lower when treated within RGD micelles as compared to treatment of free drug. On the other hand, IC50 values increased by 2 to 9 fold for micellar treatment in comparison to free drug in Detroit 551 cells. In A2058 melanoma xenograft mice model, the Paclitaxel-RGD micelles exhibited a significant inhibition of tumor growth in comparison to control treatment for both alternate day and twice weekly treatments. The studies showed the feasibility of using the non covalent peptide based self-assemblies as vehicles for targeted delivery in cancer.
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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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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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Atluri, Harisha Mitra Ashim K. "Part I: Vitreous disposition of alcohols as a function of lipophilicity part II: transporter mediated delivery of acycloguanosine antivirals to retina /." Diss., UMK access, 2004.
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Thesis (Ph. D.)--School of Pharmacy and Dept. of Chemistry. University of Missouri--Kansas City, 2004."A dissertation in pharmaceutical sciences and chemistry." Advisor: Ashim K. Mitra. Typescript. Vita. Description based on contents viewed Feb. 22, 2006; title from "catalog record" of the print edition. Includes bibliographical references (leaves 156-188). Online version of the print edition.
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Riley, Christine Marie 1964. "The effect of triacetin on solubility of diazepam and phenytoin." Thesis, The University of Arizona, 1990. http://hdl.handle.net/10150/277304.
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The effect of triacetin in combination with common cosolvents on the solubility of phenytoin and diazepam was studied. The cosolvents were PEG 400 and propylene glycol. In addition, the data were used to test the following model: UNFORMATTED EQUATION FOLLOWS: log Sᵈ(c,p,w) = log Sᵈ(w) + f(c)σᵈ(c) + [Sᵖ(w)10(f(c)σᵖ(c))/D(p)] σᵈ(p). UNFORMATTED EQUATION ENDS. The term on the left side of the equation is the solubility of a drug in the ternary system. This is related to the aqueous solubility of the drug, the solubility of the drug in a completely miscible organic solvent (CMOS), and the solubility of the partially miscible organic solvent (PMOS). This model was proposed by Gupta et al. (1989) and predicts the solubility of a ternary system composed of a CMOS and PMOS. The results indicate the triacetin does increase the solubility of the two poorly water-soluble drugs. There is good correlation between the observed and predicted increase in the solubility of the drugs.
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Liang, Wanling, and 梁婉玲. "Formulation of nucleic acid with pH-responsive amphipathic peptides for pulmonary delivery." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/207996.
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Gebremichael, Ermias. "Pharmaceutical Eutectics: Characterization and Evaluation of Tolbutamide and Haloperidol using Thermal Analytical and Complementary Techniques." Toledo, Ohio : University of Toledo, 2010. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=toledo1271439418.
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Thesis (M.S.)--University of Toledo, 2010.Typescript. "Submitted to the Graduate Faculty as partial fulfillment of the requirements of the Master of Science degree in Pharmaceutical Sciences with Industrial Pharmacy Option." "A thesis entitled"--at head of title. Title from title page of PDF document. Bibliography: p. 87-102.
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Benkorah, Amal Y. "An investigation of in vitro percutaneous penetration enhancement of benzocaine by azone, dimethylsulfoxide, and 2-pyrrolidone." Scholarly Commons, 1986. https://scholarlycommons.pacific.edu/uop_etds/494.
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This research utilizing full thickness human abdominal skin was designed to assess the in vitro percutaneous penetration of benzocaine by 1-dodecylazacycloheptan-2-one (Azone) , dimethylsulfoxide (DMSO) and 2-pyrrolidone (2-P) under conditions of constant thermodynamic activity in the vehicle. The solubilities of benzocaine in Azone and 80/20, 60/40 and 40/60 V/V DMSO/water systems were found to be 254.17, 533.00, 68.60 and 2.51 mg/ml respectively. All three adjuvants demonstrated a significant but concentration- dependent enhancement of benzocaine penetration. On the basis of comparative analysis of the steady-state fluxes, Azone was most effective at the level of 5% V/V when drug concentration was twice the saturation solubility _jn the 20/80 PG/water gel. At higher Azone levels, any penetration enhancement effects were strongly negated by a corresponding decrease in skin/vehicle partitioning. Azone appeared to enhance penetration of benzocaine molecules by directly reducing the barrier function of the stratum corneum. DMSO-induced enhancement of benzocaine penetration was observed over 40/80% V/V DMSO. Pretreatment studies strongly suggested that enhancement by DMSO is due to a significant but temporary effect on the epidermal barrier. The moderate enhancement of benzocaine penetration shown by 80% 2-P in water could be due to a decrease in diffusional resistance of stratum corneum brought on by a slow interaction between the stratum corneum and 2-P.
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Morello, A. Peter. "Novel methods of microencapsulation to improve the delivery of bioerodible nanoparticles to the gastrointestinal (GI) tract." View abstract/electronic edition; access limited to Brown University users, 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3318346.
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Zhang, Ningrong. "Trans-2-aminocyclohexanol as a pH-sensitive conformation switch in liposomes." Scholarly Commons, 2007. https://scholarlycommons.pacific.edu/uop_etds/681.
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Acid-sensitive liposome has drawn much interest as drug and gene carriers that release payloads specifically at the low-pH target sites, such as in solid tumors, tissues with inflammation, and ischemia sites. Also, it helps drug/gene to escape endosome trapping and followed lysosome degradation.
The goal of this thesis research is to develop novel trans-2-aminocyclohexanols based lipids and their liposome that can be switched by mildly acidic pH. NMR study · show that in certain acidic medium, the amine group on cyclohexane will attract proton and form hydrogen bond with the neighboring -OH. This change will force the bonds switch to from equatorial conformation to axial conformation. This conformational change is transmitted by the structure of the molecular, and induces consequently dramatic conformational change of the two long lipid tails. Fluorescence leakage assay was conducted on liposomes that encapsulated with ANTs/DPX fluorescence dyes. For certain special designed cyclohexane compounds, the pH triggered lipid conformation change will rupture liposome membrane, release the encapsulated content, and thus help them escape lysosome degradation. This would in tum improve the efficiency of liposome drug delivery and gene transfection.
Luciferase gene transfection was conducted on B16F10 cultured cells. The lipoplex comprising trans-2-aminocyclohexanollipid 1 significantly enhanced the Luciferase gene expression. The gene transfection efficiency correlated well with the pH-triggered membrane-rupture in the trans-aminocyclohexanol-based lipoplexes.
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San, Miguel Delgadillo Adriana. "Pickering emulsions as templates for smart colloidosomes." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/45760.
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Stimulus-responsive colloidosomes which completely dissolve upon a mild pH change are developed. pH-Responsive nanoparticles that dissolve upon a mild pH increase are synthesized by a nanoprecipitation method and are used as stabilizers for a double water-in-oil-in-water Pickering emulsion. These emulsions serve as templates for the production of pH-responsive colloidosomes. Removal of the middle oil phase produces water-core colloidosomes that have a shell made of pH-responsive nanoparticles, which rapidly dissolve above pH 7.
The permeability of these capsules is assessed by FRAP, whereby the diffusion of a fluorescent tracer through the capsule shell is monitored. Three methods for tuning the permeability of the pH-responsive colloidosomes were developed: ethanol consolidation, layer-by-layer assembly and the generation of PLGA-pH-responsive nanoparticle hybrid colloidosomes. The resulting colloidosomes have different responses to the pH stimulus, as well as different pre-release permeability values.
Additionally, fundamental studies regarding the role of particle surface roughness on Pickering emulsification are also shown. The pH-responsive nanoparticles were used as a coating for larger silica particles, producing rough raspberry-like particles. Partial dissolution of the nanoparticle coating allows tuning of the substrate surface roughness while retaining the same surface chemistry.
The results obtained show that surface roughness increases the emulsion stability of decane-water systems (to almost twice), but only up to a certain point, where extremely rough particles produced less stable emulsions presumably due to a Cassie-Baxter wetting regime. Additionally, in an octanol-water system, surface roughness was shown to affect the type of emulsion generated. These results are of exceptional importance since they are the first controlled experimental evidence regarding the role of particle surface roughness on Pickering emulsification, thus clarifying some conflicting ideas that exist regarding this issue.
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Dordunoo, Stephen Kwaku. "Characterization of drug-carrier systems for liquid filling of hard gelatin capsules." Thesis, Liverpool John Moores University, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.261411.
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Alyousif, Abdulmohsen A. "Examining the most economical ways in which medicines can be both presribed and dispensed in Saudi outpatient hospitals : a study carried out, exclusively in Saudi Arabian Hospitals, to determine the consraints, problems and possible solutions to effective medicines supply for outpatients." Thesis, University of Bradford, 2012. http://hdl.handle.net/10454/5696.
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Backround. Based of my personal observations when employed as a pharmacist in a Saudi hospital it was clear that there were problems with medicine supply to outpatients. This thesis was designed to scientifically investigate the types of shortages, the reason(s) for such problems and potential solutions to the problem. Methods . This study was undertaken using a variety of experimental techniques to determine the views and perceptions of patients, pharmacists, physicians and administrative staff of the hospital under examination. To establish the scale of the problem: focus groups (n=25), structured questionnaires, structured interviews/meetings for health care professionals and a national survey (n=650) were the research tools used to objectively determine the relevant data. The data were analyzed by appropriate statistical methods. Results and Discussion That there was a real problem was quickly established in the data obtained from patients. A similar finding was made for each of the 'professional groups'. The central problem was one of shortages of medicines for prescriptions presented by outpatients. It was not a case the medicines were simply not available because they were never stocked but rather a simple shortage in the dispensary stock. It was established the lack of medicines was not due to central budget arrangements but involved prescribing quantities outside of the hospital guidelines which no degree of planning could accommodate. There was also the very unexpected finding that a prescription could be filled in a variety of hospital dispensaries as individuals could access more than one hospital or they could consult more than one physician for the same condition and obtain effectively double the supplies. Communications between the hospital and patients and the health care professionals could all be improved by perhaps increasing the knowledge of the patient about the correct use of medicines. Recommendations. A series of recommendations for future work is provided
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Zhong, Sha. "Leucine-aspartic acid-valine sequence as targeting ligand & drug carrier for doxorubicin delivery to melanoma cells." Scholarly Commons, 2009. https://scholarlycommons.pacific.edu/uop_etds/2399.
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The goal of cancer chemotherapy is to develop effective, safe, and well-tolerated medications. The over-expression of certain receptors on cancer cell membrane provides a basis for active targeting by not only specific interaction between drug delivery system and cells, but also facilitated cellular uptake via receptor-mediated endocytosis. In this study, LDV oligomers up to six LDV repeating units were synthesized via solid phase peptide synthesis method, and evaluated as drug carrier as well as targeting moiety to deliver doxorubicin (Dox) to human malignant melanoma cells (A375), which over-express integrin α 4 β 1 . Cells expressing different levels of integrin α 4 β 1 or modulated using integrin α 4 -specific siRNA knock-down technique were verified by western blot and PCR. Magnetic beads with tripeptides LDV, VDL, or LNV on the surface were used in the binding specificity studies. Results verified that LDV was the minimally required ligand sequence for the specific binding to integrin α 4 β 1 , of which the interaction depends on the amount of integrin and can be utilized for the design of targeted drug delivery. The studies on A375 cells uptake of FITC-labeled LDV oligomers examined the effects of EDTA, temperature, endocytosis inhibitor, and competitive ligand. Cellular uptake mechanism was revealed to be temperature-dependent, receptor-mediated endocytosis, involving the specific interaction between LDV and integrin α 4 β 1 . The internalization extent of LDV monomer was the highest and was also inhibited to the most by the addition of free LDV when compared to other LDV oligomers. Cytotoxicity profiles of Dox-conjugated LDV oligomers were obtained on wild-type A375, integrin α4 knock-down A375, and normal human epithelial keratinocytes (NHEK) using SRB assay. A significant decrease (3∼6 folds) in the cytotoxicity of oligo(LDV)-Dox on A375 cells were observed when the integrin α4 expression was knocked down by ∼50%. Cytotoxicity further decreased on NHEK, which has the lowest integrin α4 expression among three cell lines. In contrast to oligo(LDV)-Dox, free Dox was not able to differentiate between cancerous and normal cells. This result demonstrated the potential of oligo(LDV) as targeting ligand. However, increase of repeating LDV unit did not lead to any apparent trend in cytotoxicity capacity. To facilitate the intracellular Dox release, hydrazone bond (HYD) was introduced between LDV and Dox. In vitro Dox release profiles in pH 6.0, 7.4, and rat plasma proved the pH-sensitivity of LDV-HYD-Dox. Cytotoxicity studies showed an increased cytotoxic effect of LDV-HYD-Dox when compared with LDV-Dox on wild-type A375 (2.5 times), knock-down A375 (1.5 times); while no significant difference in cytotoxicity on NHEK was observed. In vivo animal study supported the in vitro findings on LDV-HYD-Dox, which showed a significant inhibition of tumor growth and longest mice life span when compared to free Dox, poly(L,D,V)-Dox, and LDV-Dox, with averagely only ¼ of the tumor size and almost twice the life span of that from the free Dox group. In conclusion, based on the concept of specific interaction between LDV and integrin α 4 β 1 , oligo(LDV)-Dox targeted drug delivery system was developed and proved to be effective in the delivery of Dox to melanoma cells.
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Mulgaonkar, Aditi. "ASSESSMENT OF THE ROLE OF SOLUTE CARRIER DRUG TRANSPORTERS IN THE SYSTEMIC DISPOSITION OF FLUOROQUINOLONES: AN IN VITRO - IN VIVO COMPARISON." VCU Scholars Compass, 2012. http://scholarscompass.vcu.edu/etd/2842.
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Fluoroquinolones (FQ) are broad-spectrum charged antimicrobials exhibiting excellent tissue/fluid permeation. Thus, FQ disposition depends essentially on active transport and facilitative diffusion. Although most early transporter studies investigating renal elimination of FQs have focused on apical efflux of FQs from renal proximal tubule cell (RPTC) into urine, their basolateral uptake mechanism(s) from blood into RPTC (i.e., first step to tubular secretion) has not yet been explored in detail. Renally expressed SLC22 members: organic anion (OATs) and cation (OCTs) transporters are known to transport such small organic ionic substrates (molecular weight ~400 Da). Hence it is of interest to explore the role of these basolateral transporters in renal elimination of FQs, and to further quantitatively assess their impact in clinically observed FQ drug-drug interactions (DDI). An initial systematic review of clinical literature for FQs (n=18) demonstrated substantial differences among their renal clearance (CLren~46-fold) and unbound renal clearance (CLrenu~20-fold), and suggested that tubular secretion and reabsorption could be major determinants of FQ half-life, efficacy, and DDIs. FQs (n=13) identified from the above review were investigated by in-vitro transport studies using stably transfected cell lines, for potential interactions with organic cation [human (h) OCT1, hOCT2 and hOCT3] and anion [mouse (m) and hOAT3, hOAT1; and hOAT4] transporters. Further, kinetic inhibition studies were conducted to determine inhibition potency (Ki/IC50 values) for those FQs exhibiting significant OCT/OAT inhibition in preliminary interaction experiments. Gatifloxacin, moxifloxacin, prulifloxacin, and sparfloxacin were determined to be competitive inhibitors of hOCT1 with Ki = 250±18, 161±19, 136±33, and 94±8 μM, respectively. Moxifloxacin competitively inhibited hOCT3-mediated uptake, Ki = 1,598±146 μM. Enoxacin, fleroxacin, levofloxacin, lomefloxacin, moxifloxacin, prulifloxacin, and sparfloxacin exhibited competitive inhibition for mOat3 with Ki = 396±15, 817±31, 515±22, 539±27, 1356±114, 299±35, 205±12 μM, respectively. Fleroxacin and pefloxacin were found to inhibit hOAT1 with IC50 = 2228±84 and 1819±144 respectively. Despite expression in enterocytes, hepatocytes, and RPTC, hOCT3 does not appear to contribute significantly to FQ disposition. However, due to hepatic and potential RPTC expression, hOCT1 could play an important role in elimination of these antimicrobials. Among renally expressed OATs in humans, hOAT1 and hOAT3 are likely to be involved in FQ elimination.
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Khan, Ikram Ullah. "Microfluidic-assisted synthesis and release properties of multi-domain polymer microparticles drug carriers." Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAF042/document.
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Les caractéristiques et les propriétés de libération de microparticules chargées de médicament dépendent de la nature des matériaux employés, des propriétés physicochimiques des microparticules, du choix de la méthode de production, et enfin des propriétés des molécules encapsulées. A l'inverse de la plupart des méthodes conventionnelles, les méthodes microfluidiques présentent l’avantage de bien mieux contrôler la génération de gouttelettes, leur taille et leur distribution de tailles. Ainsi des dispositifs microfluidiques à base de capillaires ont été développés pour obtenir des microbilles de polymère mais également des microparticules de type janus, coeur-écorce ou troyenne, toutes monodisperses en taille et chargées de médicament(s). Ces particules ont été produites à partir de solutions de monomère qui furent polymérisées par irradiations UV de telle sorte à garder intacte l'activité des molécules chargées. Ces dispositifs peuvent être assemblés dans un court laps de temps et un simple changement dans leur conception permet d’obtenir des morphologies de particules très différentes. Ces particules ont été développées dans le but de résoudre les problèmes rencontrés dans l’administration orale de médicaments. Par exemple les microbilles peuvent être utilisées pour délivrer des anti-inflammatoires non stéroïdiens de manière continue tandis que les particules Janus peuvent libérer, simultanément et sur le même site, deux principes actifs possédant des propriétés complètement différentes (solubilité, compatibilité) également de manière prolongée. Quant aux particules coeur-écorce, elles ont été conçues pour cibler la région du côlon de l'intestin humain, et y libérer simultanément deux médicaments. Les particules troyennes furent synthétisées à l’aide d’un procédé microfluidique semi-continu qui a permis une manipulation plus sécurisée des nanoparticules vectrices ainsi que la libération continue d’un médicament dans un liquide gastrique simulé. Chaque système a été entièrement caractérisé pour assurer l’invariance entre lots et la reproductibilité. En général, la libération des ingrédients actifs a pu être facilement contrôlée/ajustée par le réglage des paramètres opératoires et de matériaux tels que les débits des différentes phases, la nature et la concentration du médicament, des (co)monomères, des agents tensioactif et de réticulation, le pH du milieu de libération. Ces différents paramètres influencent les propriétés des microparticules telles que leur morphologie, forme, taille et densité de réticulation du réseau polymèreCharacteristics and release properties of drug loaded microparticles depend upon material used and choice of production method. Conversely to most of the conventional ones, microfluidic methods give an edge by improving the control over droplet generation, size and size distribution. Capillary-based microfluidic devices were successfully used to obtain monodisperse drug(s) loaded microbeads, janus, core-shell and trojan particles using UV initiated free radical polymerization while keeping activity of active loaded molecules. These devices can be assembled in a short period of time and a slight change in design gives completely different microparticles morphologies. These particles were developed with the aim to address different issues experienced in oral drug delivery. For instance microbeads can be used to deliver NASIDs in a sustained release manner while janus particles can release two APIs with completely different properties (solubility, compatibility) also in a sustained release manner. Core-shell particles were designed to target colonic region of human intestine for dual drug delivery. Trojan particles were synthesized in a new semi-continuous microfluidic process, thus improving nanoparticles safety handling and release in simulated gastric fluid. Each system was fully characterized to insure batch to batch consistency and reproducibility. In general, the release of active ingredients was controlled by tuning the operating and material parameters like phases flow rates, nature and concentration of drug, (co)monomers, surfactant and crosslinker, pH of release media with the result of different particle morphologies, sizes and shapes or matrix crosslinking density
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Bhonsle, Amrata. "Improved Solubility and Dissolution of BCS Class II drug Spironolactone by Formulating in Ternary Solid Dispersion with Carrier Beta-Cyclodextrin and Adjuvant Water Soluble Vitamin [Pyridoxine HCl (Vit B6)]." University of Toledo Health Science Campus / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=mco1404735377.
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Bouillot, Philippe. "Copolymères diblocs amphiphiles monomethoxypolyoxyethylene-acide polylactique : synthèse et utilisation pour la fabrication de microsphères." Vandoeuvre-les-Nancy, INPL, 1997. http://www.theses.fr/1997INPL131N.
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Notre travail a porté sur la synthèse de copolymères diblocs MPOE-PLA et leur utilisation pour la préparation de systèmes de libération contrôlée, microsphères, présentant des propriétés spécifiques en raison de leur structure organisée. Nous voulions réduire l'adsorption de protéines sur la matrice en copolymère et favoriser la dégradation de celle-ci afin d'accélérer la libération du principe actif. Nous avons mis au point la synthèse de copolymères MPOE-PLA par polymérisation du lactide sur l'extrémité hydroxile du MPOE en milieu solvant et en présence d'un catalyseur, l'octoate d'étain. Nous avons utilisé cette méthode pour synthétiser une série de copolymères diblocs MPOE-PLA présentant un segment hydrophobe PLA constant (45 000 g/mole) alors que la partie hydrophile varie de 2 000 à 20 000 g/mole. Ces copolymères ont été utilisés pour préparer des microsphères contenant de la BSA comme protéine modèle par la méthode de la double émulsion. Les propriétés de ces systèmes de libération ont été étudiées et comparées à celles de microsphères en PLA. Nous avons montré que l'utilisation de copolymères diblocs conduisait à la formation d'une structure organisée avec orientation des chaines hydrophiles à la surface des microsphères et au niveau des inclusions. La longueur du segment à une influence sur la taille et la morphologie des microsphères, sur la cinétique de dégradation des microparticules et donc sur les profils de libération de la BSA, et sur le taux de BSA adsorbée à la surface des microsphères. Des copolymères diblocs tensioactifs MPOE-PLA ont également été synthétisés afin de remplacer le PVA, surfactant utilisé pour la préparation de microsphères par la double émulsion. En effet, ces copolymères MPOE-PLA sont biodégradables et bio éliminables ; les risques de toxicité dus à une accumulation dans l'organisme seront alors nuls contrairement au cas du PVA.
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Sjögren, Erik. "Hepatic Disposition of Drugs and the Utility of Mechanistic Modelling and Simulation." Doctoral thesis, Uppsala universitet, Institutionen för farmaci, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-132571.
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The elimination of drugs from the body is in many cases performed by the liver. Much could be gained if an accurate prediction of this process could be made early in the development of new drugs. However, for the elimination to occur, the drug molecule needs first to get inside the liver cell. Disposition is the expression used to encapsulate both elimination and distribution. This thesis presents novel approaches and models based on simple in vitro systems for the investigation of processes involved in the hepatic drug disposition. An approach to the estimation of enzyme kinetics based on substrate depletion data from cell fractions was thoroughly evaluated through experiments and simulations. The results that it provided were confirmed to be accurate and robust. In addition, a new experimental setup suitable for a screening environment, i.e., for a reduced number of samples, was generated through optimal experimental design. The optimization suggested that sampling at late time points over a wide range of concentration was the most advantageous. A model, based on data from primary hepatocytes in suspension, for the investigation of cellular disposition of metabolized drugs was developed. Information on the relative importance of metabolism and membrane protein related distribution was obtained by analysis of changes in the kinetics by specific inhibition of the various processes. The model was evaluated by comparing the results to those obtained from an in vivo study analyzed with an especially constructed mechanistic PBPK model. These investigations showed that the suggested model produced good predictions of the relative importance of metabolism and carrier mediated membrane transport for hepatic disposition. In conclusion, new approaches for the investigation of processes involved in hepatic disposition were developed. These methods were shown to be robust and increased the output of information from already commonly implemented in vitro systems.
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Zhou, Fanfan. "Structure-function relationship and regulation of organic anion transporters (OATS)." 2008. http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.17246.
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"Stimuli-responsive drug delivery system based on crown ether-coated, porous magnetic nanoparticles." 2011. http://library.cuhk.edu.hk/record=b5894761.
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Lee, Siu Fung.Thesis (M.Phil.)--Chinese University of Hong Kong, 2011.
Includes bibliographical references (leaves 89-91).
Abstracts in English and Chinese.
Content --- p.i
Acknowledgments --- p.iv
Abstract --- p.V
Abbreviations and Acronyms --- p.vii
Publications Originated from the Work of this Thesis --- p.ix
Chapter Chapter 1- --- Introduction
Chapter 1.1 --- Nanoparticle-based drug delivery --- p.1
Chapter 1.2 --- Magnetic nanoparticle --- p.5
Chapter 1.3 --- Iron oxide nanoparticle --- p.6
Chapter 1.3.1 --- Coprecipitation --- p.7
Chapter 1.3.2 --- Hydrothermal reaction --- p.7
Chapter 1.3.3 --- Sol-gel reaction --- p.8
Chapter 1.3.4 --- Solvothermal reaction --- p.8
Chapter 1.3.5 --- Architecture of iron oxide nanoparticles as drug carriers --- p.9
Chapter 1.4 --- Supramolecular chemistry involved in controlled release drug delivery system --- p.10
Chapter 1.5 --- Nano valve --- p.15
Chapter 1.6 --- Aim of project --- p.17
Chapter Chapter 2- --- Stimuli-Responsive Drug Delivery Nanosystems based on Fe3O4@SiO2@crown ether Nanoparticles
Chapter 2.1 --- Background --- p.19
Chapter 2.2 --- Synthesis of the dibenzo-crown ethers --- p.21
Chapter 2.3 --- Synthetic method of functionalized nanoparticles --- p.22
Chapter 2.4 --- Characterization of dibenzo-crown ethers --- p.25
Chapter 2.4.1 --- Nuclear magnetic resonance (NMR) spectroscopy --- p.25
Chapter 2.4.2 --- Mass spectrometry (MS) --- p.27
Chapter 2.4.3 --- Infrared (IR) spectroscopy --- p.28
Chapter 2.5 --- Characterization of nanoparticles --- p.29
Chapter 2.5.1 --- Transmission electron microscopy (TEM) --- p.29
Chapter 2.5.2 --- Energy-dispersive X-ray (EDX) spectroscopy --- p.34
Chapter 2.5.3 --- IR spectroscopy --- p.39
Chapter 2.5.4 --- Thermogravimetric analysis (TGA) --- p.41
Chapter 2.5.5 --- Nitrogen absorption/desorption isotherms --- p.44
Chapter 2.6 --- Biological study of functionalized nanoparticles --- p.45
Chapter 2.6.1 --- Cytotoxicity study --- p.45
Chapter 2.6.2 --- Cell adhesion study --- p.46
Chapter 2.6.3 --- Cell proliferation study --- p.47
Chapter 2.6.4 --- Cellular uptake of nanoparticles --- p.50
Chapter 2.7 --- Drug loading under different stimuli --- p.54
Chapter 2.8 --- Drug release profile of nanoparticles --- p.61
Chapter 2.9 --- MRI study of nanoparticles --- p.67
Chapter 2.10 --- Conclusion --- p.69
Chapter Chapter 3- --- Experimental Procedures
Chapter 3.1 --- General Information --- p.72
Chapter 3.2 --- General procedure of synthesis of polyethers 3a-b --- p.73
Chapter 3.2.1 --- Synthesis of 3a --- p.74
Chapter 3.2.2 --- Synthesis of 3b --- p.74
Chapter 3.3 --- General procedure of synthesis of diesters 4a-b --- p.75
Chapter 3.3.1 --- Synthesis of 4a --- p.75
Chapter 3.3.2 --- Synthesis of 4b --- p.76
Chapter 3.4 --- General procedure of synthesis of dibenzo crown ether esters 5a-c --- p.77
Chapter 3.4.1 --- Synthesis of 5a --- p.77
Chapter 3.4.2 --- Synthesis of 5b --- p.78
Chapter 3.4.3 --- Synthesis of 5c --- p.78
Chapter 3.5 --- General procedure of synthesis of dibenzo-crown ethers la-c --- p.79
Chapter 3.5.1 --- Synthesis of la --- p.80
Chapter 3.5.2 --- Synthesis of lb --- p.80
Chapter 3.5.3 --- Synthesis of lc --- p.81
Chapter 3.6 --- Preparation of superparamagnetic Fe3O4 nanoparticle with an average diameter 120 nm --- p.81
Chapter 3.7 --- Preparation of core/shell Fe3O4@SiO2 nanoparticle --- p.82
Chapter 3.8 --- Preparation of Fe3O4@SiO2@meso(CTAB)-Si02 nanoparticle --- p.82
Chapter 3.9 --- Preparation of Fe3O4@SiO2@meso(CTAB)-SiO2-NH2 nanoparticle --- p.83
Chapter 3.10 --- Preparation of Fe3O4@SiO2@meso-SiO2@crown ether(a-c) nanoparticles --- p.83
Chapter 3.11 --- Protocol of biological study of functionalized nanoparticles --- p.84
Chapter 3.11.1 --- MTT protocol --- p.84
Chapter 3.11.2 --- Cytotoxicity study --- p.84
Chapter 3.11.3 --- Cell adhesion study --- p.85
Chapter 3.11.4 --- Cell proliferation study --- p.85
Chapter 3.11.5 --- Cellular uptake of functionalized nanoparticles --- p.85
Chapter 3.12 --- Drug loading of functionalized nanoparticles --- p.86
Chapter 3.13 --- Drug release profile of functionalized nanoparticles --- p.87
Chapter 3.14 --- MRI study of nanoparticles --- p.87
References --- p.89
Appendix
List of Spectra --- p.A-1
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"Study of chitosan-based nanocarrier for drug delivery." 2011. http://library.cuhk.edu.hk/record=b5894837.
Full textAbstract:
Ng, Yiu Ming.Thesis (M.Phil.)--Chinese University of Hong Kong, 2011.
Includes bibliographical references (leaves 99-114).
Abstracts in English and Chinese.
Acknowledgements --- p.2
Abstract --- p.3
摘要 --- p.5
Content --- p.6
List of abbreviations and symbols --- p.10
Chapter Chapter 1 - --- Introduction --- p.13
Chapter 1.1 --- Introduction to nanoparticles (NPs) --- p.13
Chapter 1.2 --- How to treat solid cancers using nanoparticle drugs --- p.17
Chapter 1.3 --- What is Chitosan (CS)? --- p.22
Chapter 1.4 --- Possible peptide candidates to be trapped --- p.26
Chapter 1.4.1 --- Luffin PI - Ribosome inactivating peptide --- p.26
Chapter 1.4.2 --- Buforin lib (Bllb) - Antimicrobial peptide --- p.27
Chapter 1.5 --- Aims of study --- p.30
Chapter Chapter 2 - --- Materials and Methods --- p.31
Chapter 2.1 --- Materials --- p.31
Chapter 2.2 --- Methods --- p.31
Chapter 2.2.1 --- Construction and expression of Luffin P1 --- p.31
Chapter 2.2.2 --- Circular dichroism spectroscopy --- p.32
Chapter 2.2.3 --- Static light scattering --- p.33
Chapter 2.2.4 --- In vitro N-glycosidase assay --- p.34
Chapter 2.2.5 --- Preparation of CS particles --- p.34
Chapter 2.2.5.1 --- Preparation of positive CS NPs --- p.34
Chapter 2.2.5.2 --- Preparation of negative CS NPs --- p.35
Chapter 2.2.5.3 --- Preparation of buforin lib incorporated NPs --- p.35
Chapter 2.2.5.4 --- Preparation of Cy5 incorporated NPs --- p.36
Chapter 2.2.6 --- Characterization of CS NPs --- p.36
Chapter 2.2.7 --- Buforin lib (Bllb) encapsulation efficiency and loading capacity --- p.36
Chapter 2.2.8 --- In vitro release study --- p.37
Chapter 2.2.9 --- Confocal Microscopy --- p.37
Chapter 2.2.10 --- Cytotoxicity assay --- p.38
Chapter 2.2.11 --- Statistical analysis --- p.38
Chapter Chapter 3 - --- "Cloning, expression, purification and structural characterization of Luffin PI" --- p.39
Chapter 3.1 --- Introduction --- p.39
Chapter 3.2 --- Results --- p.41
Chapter 3.2.1 --- Construction of Luffin PI plasmid --- p.41
Chapter 3.2.2 --- Expression and purification of Luffin PI --- p.41
Chapter 3.3.3 --- Molecular weight and secondary structure determination of Luffin PI --- p.43
Chapter 3.3.4 --- 3D solution structure of Luffin PI --- p.45
Chapter 3.3.5 --- In vitro N-glycosidase activity of Luffin PI --- p.49
Chapter 3.3 --- Discussion --- p.51
Chapter Chapter 4 - --- Generation of positively charged CS particles and Bllb incorporation --- p.60
Chapter 4.1 --- Introduction --- p.60
Chapter 4.2 --- Results --- p.62
Chapter 4.2.1 --- Positively charged CS NPs generation --- p.62
Chapter 4.2.2 --- Bllb incorporated +ve CS NPs generation --- p.68
Chapter 4.2.3 --- In vitro release study --- p.70
Chapter 4.2.4 --- In vitro cytotoxicity test --- p.72
Chapter 4.3 --- Discussion --- p.74
Chapter Chapter 5 - --- Generation of negatively charged CS particles and Bllb incorporation --- p.83
Chapter 5.1 --- Introduction --- p.83
Chapter 5.2 --- Results --- p.85
Chapter 5.2.1 --- -ve CS NPs generation --- p.85
Chapter 5.2.2 --- -ve CS-Bllb NPs generation --- p.88
Chapter 5.2.3 --- In vitro release study --- p.91
Chapter 5.2.4 --- Localization study of -ve CS-Bllb NPs --- p.93
Chapter 5.2.5 --- In vitro cytotoxicity test --- p.96
Chapter 5.3 --- Discussion --- p.98
Chapter Chapter 6 - --- Conclusion and future work --- p.108
Copyright --- p.110
References --- p.111
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Hartig, Sean Michael. "Optimization of polyelectrolyte complex production implications of molecular characteristics on physicochemical and biological properties /." Diss., 2006. http://etd.library.vanderbilt.edu/ETD-db/available/etd-11132006-135117/.
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Wang, Jinzhong. "Synthesis and evaluation of novel amphiphilic macromolecules as drug carriers and therapeutics." 2007. http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.16792.
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Wu, Ke. "Developing microcomposite pharmaceutical materials using dense gas technique." 2008. http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.000050475.
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Rodrigues, Carolina Gonçalves. "Report of the Internships in Pharmaceutical Industry and Community Pharmacy and Monograph entitled "Impact of surface charged nanostructured carriers in drug delivery and targeting"." Master's thesis, 2017. http://hdl.handle.net/10316/83621.
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Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de FarmáciaUm dos maiores desafios que a tecnologia farmacêutica enfrenta nos dias de hoje diz respeito à cedência de fármacos directamente no local de acção, com o objectivo de aumentar eficácia terapêutica dos mesmos e diminuir os seus efeitos secundários. A nanotecnologia tem um papel decisivo na resposta a estas exigências, nomeadamente com o desenvolvimento de transportadores à escala nano, com as muitas vantagens e avanços que advém desta utilização. Transportadores nanoestruturados representam sistemas de cedência de fármacos com uma abordagem promissora para obter formulações de fármacos com o perfil farmacocinético e farmacodinâmico desejado. Contudo, as características dos transportadores nanoestruturados, como o tamanho, forma ou carga eléctrica de superfície irão definir a biodistribuição dos fármacos pelos diferentes órgãos. Desta forma, o estudo destas propriedades é uma prioridade, com o principal objectivo de entender o impacto destas no papel dos transportadores nanoestruturados e suas respectivas consequências. O presente trabalho disserte o impacto que a carga de superfície dos transportadores nanoestruturados tem ao nível dao direccionamento e cedência dos fármacos. Muitos estudos têm mostrado que a carga eléctrica de superfície – positiva, negativa ou neutra – pode ser o elemento chave para entender o porquê de alguns fármacos conseguirem ultrapassar a barreira hematoencefálica e outros não. Esta propriedade influencia a opsonização, tempo de circulação e interação dos fármacos com moléculas endógenas. Assim, o estudo do impacto da superfície de carga no perfil e desempenho das nanopartículas, respectivamente nos transportadores nanoestruturados e independentemente da natureza destes, é crucial no desenvolvimento de novas formulações de fármacos.
One of the biggest challenges pharmaceutical technology is dealing nowadays is the targeted delivery of drugs directly to the site of action, with the aim to increase therapeutic effectiveness and decrease adverse side effects. Nanotechnology has a decisive role while meeting these demands, namely with the development of nanostructured carriers several advantages may arise from their use. Nanostructured carriers represent drug delivery systems with a promising approach to obtain a drug formulation with the intended pharmacokinetic and pharmacodynamic profiles. Nevertheless, nanostructured carriers’ features as size, shape and surface charge will dictate the biodistribution of the drugs among the different organs. The study of these properties is therefore a priority, with the main goal of understanding their impact on the role of the nanostructured carriers and its consequences. This chapter focuses on the impact that the surface electrical charge of the nanostructured carriers has in drug delivery and targeting. As an example for understanding the importance of the design of nanoparticles for overcoming biological barriers to drug delivery, several studies have shown that different surface charge – positive, negative or neutral – may be the key element to understand why some drugs can cross the blood-brain barrier while others cannot. Or even how this property influences opsonisation, circulation life-time and interaction with endogenous molecules. Studying the impact of the surface charge on the profile and performance of nanoparticles, is therefore crucial to develop an effective drug formulation since this property has an obvious impact on the transport, delivery and release profile of the loaded drug.
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El, Sabahy Mahmoud. "Polymeric micelles as versatile carriers for drugs and nucleic acids." Thèse, 2009. http://hdl.handle.net/1866/3481.
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Le cancer est la principale cause de mortalité au Canada. Les taxanes (e.g. le paclitaxel et le docétaxel (DCTX)) constituent des remèdes efficaces contre une série de tumeurs solides telles que les cancers du sein, du poumon et de l’ovaire. Par ailleurs, des acides nucléiques (e.g. les oligonucléotides antisens (AON) ou les petits ARN interférents (siRNAs)), capables de supprimer sélectivement certains oncogènes impliqués dans la carcinogénèse, sont actuellement étudiés pour traiter une large gamme de cancers. Bien que l’activité des taxanes et des acides nucléiques soit bien établie sur des modèles humains et/ou animaux, plusieurs aspects physico-chimiques et cliniques restent encore à améliorer. Leur solubilité limitée (pour les taxanes), leur dégradation rapide dans le sang (pour les acides nucléiques), leur élimination précoce, leur absence de sélectivité et leur toxicité envers les tissus sains sont les principaux facteurs limitant leur efficacité. C’est pourquoi de nombreux efforts ont porté sur l’élaboration de systèmes de vectorisation ciblés à base de polymères, dans le but de surmonter les problèmes associés aux thérapies actuelles. Dans cette thèse, deux types de micelles polymères ont été développés pour la vectorisation de DCTX et d’acides nucléiques. D’une part, des micelles de poly(oxyde d’éthylène)-bloc-poly(oxyde de butylène/styrène) ont été étudiées pour la première fois pour solubiliser le DCTX et le protéger de l’hydrolyse. Ces polymères se sont révélés moins toxiques que le surfactant utilisé commercialement pour solubiliser le DCTX (i.e. polysorbate 80) et ont permis une libération prolongée du principe actif. D’autre part, deux systèmes différents de micelles polyioniques (PICM) ont été mis au point pour la vectorisation d’acides nucléiques. De nouveaux conjugués de poly(éthylène glycol) (PEG)-oligonucléotide ont été proposés pour la protection et la libération contrôlée d’AON. Lorsque ces conjugués ont été formulés avec des dendrimères de poly(amidoamine) (PAMAM), des complexes de taille homogène ont été obtenus. Ces PICM ont permis de prolonger la libération de l’AON et de le protéger efficacement contre la dégradation enzymatique. De plus, des polymères de poly(oxyde d’éthylène)-bloc-poly(méthacrylate de propyle-co-acide méthacrylique) ont été incorporés afin de conférer des propriétés acido-sensibles aux PICM. Dans ces micelles, formées de ce dernier polymère formulé avec le dendrimère PAMAM, des oligonucléotides (AON et siRNA) ciblant l’oncogène Bcl-2 ont été encapsulés. L’internalisation cellulaire fut assurée par un fragment d’anticorps monoclonal (Fab’) situé à l’extrémité de la couronne de PEG. Après l’internalisation cellulaire et la protonation des unités d’acide méthacrylique sous l’effet de l’acidification des endosomes, les micelles se sont affranchies de leur couronne. Elles ont ainsi exposé leur cœur composé d’acide nucléique et de dendrimère PAMAM, qui possède une charge positive et des propriétés endosomolytiques. En effet, ces PICM acido-sensibles ciblées ont permis d’augmenter la biodisponibilité des acides nucléiques vectorisés et se sont avérées plus efficaces pour silencer l’oncoprotéine Bcl-2 que les micelles non ciblées ou que le dendrimère de PAMAM commercial seul. Finalement, les nanovecteurs polymères présentés dans cette thèse se révèlent être des systèmes prometteurs pour la vectorisation des anticancéreux et des acides nucléiques.Cancer is considered as the leading cause of premature death in Canada. Taxanes (e.g. paclitaxel and docetaxel (DCTX)) are effective against a range of solid tumors including breast, lung, and ovarian malignancies. In addition, nucleic acids (e.g. antisense oligonucleotides (AON) and short interfering RNA (siRNA)) which are capable of selectively suppressing oncogenes involved in carcinogenesis are currently being investigated for the treatment of a wide variety of cancers. Although the activity of taxanes and nucleic acid drugs is well-established in human and/or animal models, several physicochemical and clinical issues still need to be addressed. Low aqueous solubility (i.e. taxanes), rapid degradation in the blood (i.e. nucleic acids), fast clearance, non-selectivity and toxicity to normal tissues are limiting factors to their effectiveness. Hence, many efforts have been focused on developing targeted polymeric delivery systems to overcome the problems associated with the current therapies. In this thesis, two types of polymeric micelles have been developed for the delivery of DCTX and nucleic acids. On the one hand, poly(ethylene oxide)-block-poly(butylene oxide/styrene oxide) micelles were tested for the first time to solubilize and protect DCTX from hydrolytic degradation. The polymers showed less toxicity than the surfactant used commercially to dissolve DCTX (i.e. polysorbate 80) and released the drug in a sustained fashion. On the other hand, two different systems of polyion complex micelles (PICM) were developed for the sustained release and intracellular delivery of nucleic acids. Novel poly(ethylene glycol) (PEG)-oligonucleotide conjugates were assessed to protect AON against degradation and release them in a sustained manner. When these conjugates were mixed with poly(amidoamine) (PAMAM) dendrimers, monodisperse PICM were formed. These PICM further slowed down AON release and significantly protected it against enzymatic degradation. In addition, the incorporation of poly(ethylene oxide)-block-poly(propyl methacrylate-co-methacrylic acid) was exploited to impart pH-sensitivity to PAMAM-based PICM. This system was composed of the previous copolymer mixed with PAMAM dendrimer. Such PICM were loaded with AON or siRNA targeting the Bcl-2 oncogene. Micelles uptake by the cancer cells was mediated by a monoclonal antibody fragment (i.e. Fab') positioned at the extremity of the PEG corona. Upon cellular uptake and protonation of the methacrylic acid units in the acidic endosomal environment, the micelles lost their corona, thereby exposing their positively-charged endosomolytic PAMAM/nucleic acid core. The targeted, pH-sensitive PICM were found to increase the intracellular bioavailability of the entrapped nucleic acids and knock down the Bcl-2 oncoprotein more than either non-targeted micelles or commercial PAMAM dendrimers. The polymeric nanocarriers reported in this thesis appear to be promising vehicles for the delivery of anticancer drugs and nucleic acids.
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Han, Xu. "Identification and mechanistic investigation of clinically important myopathic drug-drug interactions." Thesis, 2014. http://hdl.handle.net/1805/5275.
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Indiana University-Purdue University Indianapolis (IUPUI)Drug-drug interactions (DDIs) refer to situations where one drug affects the pharmacokinetics or pharmacodynamics of another. DDIs represent a major cause of morbidity and mortality. A common adverse drug reaction (ADR) that can result from, or be exacerbated by DDIs is drug-induced myopathy. Identifying DDIs and understanding their underlying mechanisms is key to the prevention of undesirable effects of DDIs and to efforts to optimize therapeutic outcomes. This dissertation is dedicated to identification of clinically important myopathic DDIs and to elucidation of their underlying mechanisms. Using data mined from the published cytochrome P450 (CYP) drug interaction literature, 13,197 drug pairs were predicted to potentially interact by pairing a substrate and an inhibitor of a major CYP isoform in humans. Prescribing data for these drug pairs and their associations with myopathy were then examined in a large electronic medical record database. The analyses identified fifteen drug pairs as DDIs significantly associated with an increased risk of myopathy. These significant myopathic DDIs involved clinically important drugs including alprazolam, chloroquine, duloxetine, hydroxychloroquine, loratadine, omeprazole, promethazine, quetiapine, risperidone, ropinirole, trazodone and simvastatin. Data from in vitro experiments indicated that the interaction between quetiapine and chloroquine (risk ratio, RR, 2.17, p-value 5.29E-05) may result from the inhibitory effects of quetiapine on chloroquine metabolism by cytochrome P450s (CYPs). The in vitro data also suggested that the interaction between simvastatin and loratadine (RR 1.6, p-value 4.75E-07) may result from synergistic toxicity of simvastatin and desloratadine, the major metabolite of loratadine, to muscle cells, and from the inhibitory effect of simvastatin acid, the active metabolite of simvastatin, on the hepatic uptake of desloratadine via OATP1B1/1B3. Our data not only identified unknown myopathic DDIs of clinical consequence, but also shed light on their underlying pharmacokinetic and pharmacodynamic mechanisms. More importantly, our approach exemplified a new strategy for identification and investigation of DDIs, one that combined literature mining using bioinformatic algorithms, ADR detection using a pharmacoepidemiologic design, and mechanistic studies employing in vitro experimental models.
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HU, MING. "INVESTIGATION INTO DRUG AND DRUG ANALOGS TRANSPORTED BY THE PEPTIDE CARRIER SYSTEM: INTESTINAL ABSORPTION OF CAPTOPRIL AND OF PEPTIDYL DERIVATIVES OF METHYLDOPA." 1988. http://catalog.hathitrust.org/api/volumes/oclc/68300068.html.
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SINKO, PATRICK JOHN. "PREDICTING ORAL DRUG ABSORPTION IN MAN FOR COMPOUNDS ABSORBED BY CARRIER MEDIATED AND PASSIVE ABSORPTION PROCESSES." 1988. http://books.google.com/books?id=pk9tAAAAMAAJ.
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Mukherjee, Mousumi Beto. "Application of Mesoporous Silica nanoparticles as a nano-carrier for the treatment of HCV and HIV infections." Thesis, 2020. https://etd.iisc.ac.in/handle/2005/4964.
Full textAbstract:
Carrier-mediated drug delivery systems have emerged as a powerful tool for the treatment of various diseases, especially, in the field of viral infection. The therapeutic index of traditional and novel anti-virals are heightened through the enhancement in their target specificity. Anti-virals can be delivered at the targeted site without any degradation with the support of a nano-carrier. Viral disease treatment needs an upgraded drug delivery system to reduce the dosage and systemic toxic effects along with improved pharmacokinetic properties of anti-viral therapeutics.
In this thesis, mesoporous silica nanoparticle (MSN) based delivery system was synthesized to deliver therapeutic agents to increase their efficiency and bioavailability. Functionalization was carried as per the requirement. The synthesized delivery vector was characterized using different techniques. The ability of MSN to interact with therapeutic agents was also evaluated. Toxicity studies using cell cultures and animal models assured the non-toxic properties of this delivery vector. The as prepared nanocarrier was able to mediate efficient transfection in mammalian cells. Preferential delivery of drugs was proven using both in vitro as well as in vivo models confirming the target-specific nature of this MSN based delivery system.
Targeted delivery of small hairpin DNA (shDNA) to liver using MSN based nano-carrier to combat hepatitis C virus (HCV) infection was investigated. MSN was amine functionalized to achieve electrostatic interaction between the nanoparticle and DNA. Galactose functionalization ensured the preferential delivery to the liver through the ligand asialoglycoprotein receptor interaction abundantly present on liver cell surface which was visualized in the in vivo model. Significant reduction (about 94 %) of viral RNA level was achieved which confirmed the successful delivery and action of the shDNA.
Target specific property of as-synthesized nanoparticle was further expanded in delivering the two herbal compounds Phyllanthin and Corilagin in HCV infection. These herbal compounds were derived from natural source Phyllanthus amarus and shown to have hepatoprotective property. The delivery of herbal compound-nanoparticle complex to the HCV JFH-1 infectious virus systems resulted in ~93% decrease in viral RNA level which was 3-fold higher than free Phyllanthin or Corilagin.
Further this MSN based nano-carrier was used to enhance the bioavailability of retro-viral drugs. Here in this work MSN was coated with chitosan to inhibit the premature release of drugs and increase the cellular uptake. The amount of drug loaded in MSN was found to be 76.91 %. On applying the drug loaded nanocarrier in Balb/c mice model a 2.4-fold increase in bioavailability was noted.
The work described in the present thesis presents a new MSN based delivery system which can act as an efficient nano-carrier both in gene delivery and drug delivery for virus infected diseases.