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1
Castro-Lopez, Vanessa. "Colloidal microgels as (trans)dermal drug delivery systems." Thesis, University of Greenwich, 2005. http://gala.gre.ac.uk/6230/.
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In this study microgels have been used as novel drug carriers (i.e. a novel controlled drug delivery system) for either dermal or transdermal delivery. The experiments conducted in this project were, firstly, to investigate the uptake and release of model compounds with different physico-chemical properties (i.e. solubility and logKoct/w) to and from two colloidal gel systems. Secondly, the permeation of model compounds across a model skin membrane (silicone membrane), and human epidermis was investigated. The first part of the project was to co-synthesise temperature-sensitive colloidal microgels particles based on a co-polymer of poly(N-isopropylacrylamide) (90%)-co-butyl acrylate (10%) (NIPAM/BA) (90/10)(w/w)%, in the presence of and in the absence of ibuprofen (IBU), methyl paraben (MP), and propyl paraben (PP), by a surfactant-free emulsion polymerisation (SFEP) in water. Physico-chemical properties of the microgels were determined using different techniques including photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), nuclear magnetic resonance (NMR spectroscopy), and turbidimetric analysis (UV-vis). The uptake and release of the model compounds to and from colloidal microgel particles was controlled by the solubility and logKoct/w of the drugs. Their subsequent permeation across a model silicone membrane and human skin, were investigated over a range of temperatures (292 K – 313 K). The transport rate of IBU and, PP from poly(NIPAM) microgel is significantly reduced by two and one order of magnitude, respectively, compared with the transport rate of saturated solutions. A huge reduction in the flux indicates that the microgel retards permeation of the drug across both membranes, and hence the microgel can be considered as a permeation retarder. However, fluxes of MP from poly(NIPAM) microgel are equivalents to fluxes of saturated solutions of MP. There is a clear correlation between the solubility and logKoct/w value of the drugs and the flux value for the microgels, incorporating the drugs, across both types of membranes. In the second part of the work, a co-polymer of poly(NIPAM) (85%) co-butyl acrylate (10%) co-methacrylic acid (5%) (NIPAM/BA/MAA) (85/10/5) microgel was synthesised and investigated as a potential pH and temperature sensitive transdermal delivery device. Three compounds having different logKoct/w and solubilities were incorporated into the microgel, namely: salicylamide (SA), methyl paraben and propyl paraben.
2
Tison, Christopher Kirby. "Programmable, isothermal disassembly of DNA-linked colloidal particles." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/28189.
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Thesis (M. S.)--Materials Science and Engineering, Georgia Institute of Technology, 2009.Committee Chair: Milam, Valeria; Committee Member: Boyan, Barbara; Committee Member: Li, Mo; Committee Member: McDevitt, Todd; Committee Member: Sandhage, Ken.
3
Fiebrig, Immo. "Solution studies on the mucoadhesive potential of various polymers for use in gastrointestinal drug delivery systems." Thesis, University of Nottingham, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.307747.
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Dennis, Andrew C. "Studies of some molecular reorganisations in the solid state and in colloidal media by vibrational spectroscopy." Thesis, Queen's University Belfast, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.322846.
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Karmakar, Gourab. "Physicochemical investigation on Nanostructural Lipid Carriers." Thesis, University of North Bengal, 2018. http://ir.nbu.ac.in/handle/123456789/2855.
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Corvari, Susan Jane. "The implications of physical stability on orally administered colloidal drug delivery systems and cyclosporin A absorption /." Ann Arbor, Mich. : UMI, 1992. http://www.gbv.de/dms/bs/toc/016076850.pdf.
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Swami, Salesh N., University of Western Sydney, of Science Technology and Environment College, and of Science Food and Horticulture School. "Radiation synthesis of polymeric hydrogels for swelling-controlled drug release studies." THESIS_CSTE_SFH_Swami_S.xml, 2004. http://handle.uws.edu.au:8081/1959.7/698.
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Hydrogels are three dimensional networks of hydrophilic homopolymers or copolymers generally covalently or ionically crosslinked. They interact with aqueous media by swelling to some equilibrium value by retaining the aqueous media in their structures. This study concerns the investigation of the swelling and the controlled drug release behaviour of hydrogels synthesized via the photopolymerisation process. The study of hydrogels in this project was oriented towards their biomedical applications as controlled drug delivery devices. It is a known fact that the complete conversion of monomers to polymers may not be achieved in the polymerisation process thus there is always a certain component of unreacted toxic monomers still remained in the polymer matrix. These monomers have the tendency to leach out of the polymer matrices when the polymers are in contact with an aqueous medium thus rendering the hydrogel to be nonbiocompatable. The polymers synthesized in this work were washed thoroughly in milli-Q-water and then evaluated in vitro for any possible toxic effect on human keratinocyte (HaCaT)v cells using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diaphenyl tetrazolium bromide (MTT) cell proliferation assay. The cytotoxicity results indicated that the hydrogels understudy sustained and allowed a positive growth of the HaCat cells in the duration of the cytotoxicity experiment, thus proving to be satisfactorily compatible.Doctor of Philosophy (PhD)
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Blackburn, William H. "Microgel bioconjugates for targeted delivery to cancer cells." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2008. http://hdl.handle.net/1853/31792.
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Thesis (Ph.D)--Chemistry and Biochemistry, Georgia Institute of Technology, 2009.Committee Chair: Lyon, L. Andrew; Committee Member: Barry, Bridgette; Committee Member: Fahrni, Christoph J.; Committee Member: Hud, Nicholas V.; Committee Member: Le Doux, Joseph M. Part of the SMARTech Electronic Thesis and Dissertation Collection.
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Tuesca, Anthony D. Lowman Anthony M. "Synthesis, characterization, and application of polyethylene glycol modified insulin for oral delivery using complexation hydrogels /." Philadelphia, Pa. : Drexel University, 2008. http://hdl.handle.net/1860/2715.
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Swami, Salesh N. "Radiation synthesis of polymeric hydrogels for swelling-controlled drug release studies." Thesis, View thesis, 2004. http://handle.uws.edu.au:8081/1959.7/698.
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Hydrogels are three dimensional networks of hydrophilic homopolymers or copolymers generally covalently or ionically crosslinked. They interact with aqueous media by swelling to some equilibrium value by retaining the aqueous media in their structures. This study concerns the investigation of the swelling and the controlled drug release behaviour of hydrogels synthesized via the photopolymerisation process. The study of hydrogels in this project was oriented towards their biomedical applications as controlled drug delivery devices. It is a known fact that the complete conversion of monomers to polymers may not be achieved in the polymerisation process thus there is always a certain component of unreacted toxic monomers still remained in the polymer matrix. These monomers have the tendency to leach out of the polymer matrices when the polymers are in contact with an aqueous medium thus rendering the hydrogel to be nonbiocompatable. The polymers synthesized in this work were washed thoroughly in milli-Q-water and then evaluated in vitro for any possible toxic effect on human keratinocyte (HaCaT)v cells using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diaphenyl tetrazolium bromide (MTT) cell proliferation assay. The cytotoxicity results indicated that the hydrogels understudy sustained and allowed a positive growth of the HaCat cells in the duration of the cytotoxicity experiment, thus proving to be satisfactorily compatible.
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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, and 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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Nolan, Christine Marie. "Microgel Based Materials for Controlled Macromolecule Delivery." Diss., Georgia Institute of Technology, 2005. http://hdl.handle.net/1853/6874.
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This dissertation focuses on utilization of poly(N-isopropylacylamide) (pNIPAm) based mirogels for regulated macromolecule drug delivery applications. There is particular emphasis on incorporation of stimuli responsive materials into multi-layer thin film constructs with the main goal being fabrication of highly functional materials with tunable release characteristics. Chapter 1 gives a broad overview of hydrogel and microgel materials focusing on fundamental properties of pNIPAm derived materials. Chapter 2 illustrates the progression of controlled macromolecule release from hydrogel and microgel materials and sets up the scope of this thesis work. Chapter 3 details studies on thermally modulated insulin release from microgel thin films where extended pulsatile release capabilities are shown. Chapters 4 and 5 focus on more fundamental synthesis and characterization studies of PEG and acrylic acid modified pNIPAm microgels that could ultimately lead to the design of protein loaded microgel films with tunable release characteristics. Chapter 6 illustrates fundamental macromolecule loading strategies, which could also prove useful in future protein drug delivery design using stimuli responsive networks. Chapter 7 concentrates on direct insulin release studies that probe the interaction between entrapped and freely diffusing protein and microgels. These model experiments could prove useful in design of tunable macromolecule drug release from functionally modified microgels and could aid in the tailored design of peptide-loaded microgel thin films. Chapter 8 discusses the future outlook of controlled macromolecule release from microgel based materials.
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Smith, Michael Hughes. "The design of multifunctional hydrogel nanoparticles for drug delivery." Diss., Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/43609.
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Hydrogel micro- and nanoparticles (microgels and nanogels) are a promising class of drug delivery vehicles. Composed of hydrophilic polymers arranged into a cross-linked network structure, nanogels show several attractive features for the delivery of macromolecule therapeutics. For instance, the hydrated, porous internal cavity of the nanogel may serve as a high capacity compartment for loading macromolecules, whereas the periphery of the nanogel may be used as a scaffold for conjugating cell-specific targeting moieties. This dissertation presents recent investigations of nanogels as targeted delivery vehicles for oligonucleotides to cancer cells, while exploring new nanogel chemistries that enable future in vivo applications. For instance, synthetic efforts have produced particles capable of erosion into low molar mass constituents, providing a possible mechanism of particle clearance after repeated administration in vivo. In another example, the microgel network chemistry was tuned to promote the encapsulation of charged proteins. In parallel with those synthetic efforts, new light scattering methodologies were developed to accurately quantify the particle behaviors (e.g. loading, erosion). Using multiangle light scattering (MALS), changes in particle molar mass and radius were measured, providing a quantitative and direct approach for monitoring nanogel erosion and macromolecule encapsulation. The new particle chemistries demonstrated, together with enabling light scattering methods, will catalyze the development of improved delivery vehicles in the near future.
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Shriky, Banah. "Thermosensitive Injectable Pluronic Hydrogels for Controlled Drug Release: Characterisation of thermal, rheological and structural properties of injectable pharmaceutical formulations." Thesis, University of Bradford, 2018. http://hdl.handle.net/10454/17364.
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This study seeks to develop smart hydrogel formulations for injectable controlled drug delivery from Pluronics to enhance patients compliance, decrease side effects, reduce dose and frequency.
A biocompatible copolymer, Pluronic F127 was probed as the main ingredient for the injectable systems owing its low gelation concentration and ease of modification the system properties through excipients addition. The matrix properties were studied through a series of thermal, rheological and structural (SAXS/SANS) experiments as a function of concentration and shear rate, covering both static and dynamic environments. It has shown that gelled viscosity (and structure) can be critically controlled by shear rate and the structures recorded do not match those predicted for sheared colloids. Two further Pluronics F68 and F108, were studied showing similar but shifted gelation properties to F127.
Effects of additives were studied by introducing different Mw PEGs and a model hydrophobic drug ‘ibuprofen’ to a F127 20% formulation. PEGs addition effects on the system properties and gelation transition were largely dependent on the Mw used in the blend, which became more prominent with increasing chain length.
Ibuprofen’s addition has resulted in reduced gelation temperature and smaller hard spheres without having a great effect on the system rheological properties compared to neat gels.
Blends containing both additives PEG and ibuprofen exhibited a synergistic effect, where comparisons show that Ibuprofen had the largest effect on the blends lowering gelation boundaries and slightly increasing the size of the hard spheres indicating the necessity of full characterisation of the formulation with any API.
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Brindley, Anne. "The preparation and characterization of model polymer colloids for potential site-specific drug delivery systems." Thesis, University of Nottingham, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335470.
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Swami, Salesh N. "Radiation synthesis of polymeric hydrogels for swelling-controlled drug release studies." View thesis, 2004. http://library.uws.edu.au/adt-NUWS/public/adt-NUWS20050729.124150/index.html.
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Liang, Ya Palmese Giuseppe R. Lowman Anthony M. "Functional polymer-polymer composites by nano/meso-fiber encapsulation : applications in drug delivery systems and polymer toughening /." Philadelphia, Pa. : Drexel University, 2010. http://hdl.handle.net/1860/3316.
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Serpe, Michael Joseph. "Self-Assembly of Poly(N-isopropylacrylamide) Microgel Thin Films." Diss., Georgia Institute of Technology, 2004. http://hdl.handle.net/1853/4806.
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The assembly of poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAm-co-AAc) microgel thin films into disordered and ordered arrays was investigated. Disordered pNIPAm-co-AAc microgel arrays were assembled based on electrostatic attractions between polyanionic pNIPAm-co-AAc microgels and polycationic poly(allylamine hydrochloride) (PAH). These interactions were studied in solution and subsequently used to assemble thin films following a Layer-by-Layer assembly protocol. Thin films were assembled as a function of pNIPAm-co-AAc microgel solution temperature and the resultant film thermoresponsivity characterized as a function of microgel layer number and pH. The response of assembled thin films to pH 3.0 and 6.5 exposure was then characterized by quartz crystal impedance and surface plasmon resonance spectroscopy, which showed that the thin film solvation was highly dependent on the pH of the solution it was in. Assembled thin films were also shown to be useful as controlled drug delivery platforms, where it was found that small molecules could be released from the films in a temperature regulated fashion. Microgel thin films also exhibited unique optical properties and were used as microlens arrays, which were able to focus pattern in air as well as in solution and had focal lengths that could be tuned in response to pH and temperature changes. Ordered microgel arrays were assembled following a thermal annealing process, in order to make light diffracting materials. These ordered arrays were photopolymerized and exhibited temperature dependent Bragg diffraction properties.
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Fraylich, Michael. "Colloidal delivery systems." Thesis, University of Manchester, 2010. https://www.research.manchester.ac.uk/portal/en/theses/colloidal-delivery-systems(4db13949-85d3-434e-a3dd-5d713b66aff2).html.
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In this project we aim to produce a thermally triggered PLGA particulate gel, which is injectable and biocompatible. This will act as a scaffold for soft tissue repair. Three coating polymers were tested: Pluronics (PEG-PPG-PEG), poly(PPGMA-co-PEGMA) and poly(PNIPAm-DMA+). These were first tested as a dilute solution for clouding behaviour and then added to PLGA nanoparticles dispersions and tested rheologically for gel behaviour. These three polymers were chosen for their amphiphilic nature which may allow for surface attachment and decreasing miscibility with temperature. The PLGA copolymer in this work contained 75% lactic acid and 25% glycolic acid, and was made into a nanoparticle dispersion by interfacial deposition. The Pluronic L62 showed a promising cloud point temperature (Tclpt) of 37 °C, but did not show gel behaviour with the PLGA dispersions. It conferred thermally triggered aggregation, which may be useful as a drug delivery system. The poly(PPGMA-PEGMA) was synthesised using a free radical polymerisation feed method. These copolymers showed promising Tclpt values (20-37 °C) but only showed increased viscosity when heated at high concentration and when mixed with a PLGA dispersion. The structure-property relationships for these copolymers were analysed. Poly(NIPAM-DMA+) showed gelation at low concentrations without the particles, when the particle dispersion was added the gel maintained its strength up to 300% strain. This is unlike most particulate gels which tend to be brittle. Using cell culture the biocompatibility of these gels was tested. After 72 hours the cells appeared healthy and to be proliferating.
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Albasarah, Yaqoub Yousif. "Colloidal carriers for nebulized drug delivery." Thesis, University of London, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.553758.
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Objectives: To explore the potential of liposomes, chitosan-coated liposomes and chitosan complexes for pulmonary delivery of hydrophilic and hydrophobic materials using medical nebulizers. Methods: Chitosan coated and uncoated liposomal vesicles containing the hydrophobic drug amphotericin B (AmB) or hydrophilic lactate dehydrogenase (LDH) were generated from ethanol-based proliposomes and by thin film hydration. LDH chitosan complexes were prepared using different molecular weights and concentrations of the polymer. The colloidal formulations were assessed for morphology, particle size and surface charge. A twin stage impinger (TSI) was used to determine aerosol deposition following delivery from air-jet, ultrasonic and vibrating-mesh nebulizers. Differential scanning calorimetry (DSC) was used to examine the interaction between some formulation components. Main results: AmB incorporation was highest for vesicles produced from proliposomes. Following nebulization, approximately 60% of the AmB was deposited in the lower stage of TSl. Chitosan-coated and uncoated liposomes had antifungal activities against Candida albicans and Candida tropicalis with a minimum inhibitory concentration of 0.5 mg/ml. The highest molecular weight chitosan had the greatest complex size and a net positive charge of +29.7 mY. Nebulization ofLDH solution resulted in enzyme denaturation and greatly reduced activity. Enzyme stability was improved in liposomal formulations and chitosan complexes compared to LDH in solution with greater than 50% of the LDH in a nebulizer delivered to the lower stage of the TSI, with greater than 60% retained activity. DSC analysis suggested that the interaction between LDH and liposomes was electrostatic, with no penetration into vesicle bilayers. Conclusions: This study has demonstrated the potential of liposomes, chitosan-coated liposomes and chitosan complexes to enhance aerosol delivery of associated materials. Liposomal vesicles of AmB had a high drug-loading that is likely to be effectively delivered to the peripheral airways for treatment of pulmonary fungal infections. Chitosan complexes and liposomes containing LDH provided an effective means of increasing the stability of the labile enzyme to nebulization.
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Ward, Keeran. "The application of colloidal liquid aphrons for drug delivery." Thesis, Imperial College London, 2015. http://hdl.handle.net/10044/1/52445.
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Colloidal Liquid Aphrons (CLAs) have been used in a variety of applications ranging from detergency and solute extraction, to enzyme immobilisation, and have been shown to have very high mass transfer areas due to their size (5-20μm). Also, due to their structure they are very stable while also being naturally buoyant in aqueous solutions, providing natural homogeneity. Over the last few decades their use in the laboratory as an immobilisation support for enzymatic catalysis has been extensive due to their stability, and ability to promote superactivity. Due to these specific characteristics, the possibility of using CLAs as a stable formulation for drug delivery has been particularly attractive. However, in an effort to apply existing research to the area of drug delivery, a new formulation methodology was developed utilizing non-ionic surfactants, nonpolar solvents, and model proteins as active pharmaceutical ingredients with varying molecular weights and isoelectric points (pI). Insights into the chemical forces governing immobilisation showed that hydrophobic interactions were primarily responsible for binding. Adsorption was the main mechanism for immobilisation, with higher affinities being observed with increasing protein concentration and smaller particle size. Superactivity was observed with Lipase and α-chymotrypsin, while aprotinin retained 85% of its inhibitor potency. Evaluation of immobilised enzyme conditions showed that non-ionic CLAs preserved natural pH and temperature optima, while thermodynamic evaluations of activity suggested that the presence of water molecules lead to an active conformation. Characterisation studies on refractive index matched polyaphron systems showed that proteins interacted mainly with the ‘’soapy-shell’’ leading to a hydrated conformation, while calorimetric studies on nonionic surfactant binding proved that surfactant interactions were virtually non-existent. Desorbed enzymes regained their natural conformation illustrating that any small structural effects were reversible upon release. The use of sodium alginate as an additive for enhanced immobilisation proved successful due to induced electrostatic interactions when the pH was lower than the protein pI. Conformational effects upon binding with sodium alginate also proved to be reversible, with an increase in the concentration of the released protein being observed when the pH was >pI. However, the extent of electrostatic interactions on the bioactivity of released proteins was found to be non-denaturing with hydrophilic enzymes, while hydrophobic enzymes were more active upon binding. Finally, insights into proteolytic digestion suggest that electrostatic interactions lead to greater protease vulnerability due to conformational changes induced upon binding.
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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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Roberts, Mark J. J. "The production and characterization of a model microparticulate oral antigen delivery system." Thesis, University of Nottingham, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.291890.
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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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Riley, Trevor. "Physicochemical evaluation of nanoparticles assembled from block copolymers as colloidal drug carriers." Thesis, University of Nottingham, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298036.
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Lin, Wu. "The preparation and characterization of surface modified albumin nanoparticles for site specific drug delivery." Thesis, University of Nottingham, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336920.
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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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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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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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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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