Dissertations / Theses on the topic 'Lipid based delivery systems'
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Mok, Kenneth W. C. "Characterization of lipid-based DNA delivery systems." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ34590.pdf.
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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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Brinkmann, Joscha [Verfasser]. "Thermodynamics of Lipid-Based Drug Delivery Systems / Joscha Brinkmann." München : Verlag Dr. Hut, 2021. http://d-nb.info/1238423043/34.
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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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Lam, Angela Man Iu. "Influence of calcium on the transfection properties of lipid-based gene delivery systems." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/NQ61130.pdf.
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Kleemann, Elke. "Polyethylenimine- and lipid-based nanoparticles as gene and drug delivery systems for aerosol therapy to the lung." [S.l.] : [s.n.], 2005. http://archiv.ub.uni-marburg.de/diss/z2005/0363/.
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Helena, (nee Slabbert) Chrizaan. "Formulation, characterization and cellular toxicity of lipid based drug delivery systems for mefloquin / Chrizaan Helena (nee Slabbert)." Thesis, North-West University, 2011. http://hdl.handle.net/10394/8433.
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Malaria affects millions of people annually especially in third world countries. Increase in resistance and limited research being conducted adds to the global burden of malaria. Mefloquine, known for unwanted adverse reactions and neurotoxicity, is highly lipophilic and is still used as treatment and prophylaxis. Lipid drug delivery systems are commonly used to increase solubility and efficacy and decrease toxicity. The most generally used lipid drug delivery system is liposomes. The lipid bilayer structure varying in size from 25 nm to 100 μm can entrap both hydrophilic and lipophilic compounds. Similar in structure and size to liposomes, Pheroid™ technology consist of natural fatty acids and is also able to entrap lipophilic and hydrophilic compounds. The aim of this study was to formulate liposomes and Pheroid™ vesicles loaded with mefloquine and evaluate the physiochemical characteristic of the formulations followed by efficacy and toxicity studies. Pheroid™ vesicles and liposomes with and without mefloquine were evaluated in size, morphology, pH and entrapment efficacy during three month accelerated stability testing. Optimization of size determination by flow cytometry lead to accurate determination of size for both Pheroid™ vesicles and liposomes. During the three months stability testing, Pheroid™ vesicles showed a small change in size from 3.07 ± 0.01 μm to approximately 3 μm for all three temperatures. Confocal laser scanning microscopic evaluation of the liposomes showed structures uniform in spherical shape and size. No difference in size or structure between the Pheroid™ vesicles with and without mefloquine were obtained. Significant increase (p=0.027) in size from 6.46 ± 0.01 μm to above 10 μm was observed for liposomes at all the temperatures. Clearly formed lipid bilayer structures were observed on micrographs. With the addition of mefloquine to the liposome formulation, a decrease in the amount of bilayer structures and an increase in oil droplets were found. Entrapment efficacy was determined by firstly separating the entrapped drug from the unentrapped drug utilizing a Sephadex®G50 mini column. This was followed by spectrophotometric evaluation by UV-spectrophotometry at 283 nm. Initial entrapment efficacy of both Pheroid™ vesicles and liposomes was above 60%. An increase in entrapment efficacy was observed for Pheroid™ vesicles. The addition of mefloquine to already formulated Pheroid™ vesicles illustrated entrapment efficacy of 60.14 ± 5.59% after 14 days. Formulations loaded with mefloquine resulted in lower pH values as well as a decrease in pH over time. Optimization of efficacy studies utilizing propidium iodide was necessary due to the similarity in size and shape of the drug delivery systems to erythrocytes. A gating strategy was successfully implemented for the determination of the percentage parasitemia. Efficacy testing of mefloquine loaded in Pheroid™ vesicles and liposomes showed a 186% and 207% decrease in parasitemia levels compared to the control of mefloquine. Toxicity studies conducted include haemolysis and ROS (reactive oxygen species) analysis on erythrocytes as well as cell viability on mouse neuroblastoma cells. Pheroid™ vesicles with and without mefloquine resulted in a dose dependent increase in ROS and haemolysis over time. A dose dependent increase in ROS and haemolysis in both liposome formulations were observed, but to a lesser extent. Mefloquine proved to be neurotoxic with similar results obtained when mefloquine was entrapped in liposomes. Pheroid™ vesicles seem to have neuroprotective properties resulting in higher cell viability. Mefloquine could be entrapped successfully in Pheroid™ vesicles and less in liposomes. Pheroid™ vesicles was more stable over a three months accelerated stability testing with more favourable characteristics. The increase in ROS levels of Pheroid™ vesicles could be responsible for the higher efficacy and haemolytic activity. DL-α-Tocopherol in Pheroid™ vesicles possibly acted as a pro-oxidant due to the presence of iron in the erythrocytes. DL-α-Tocopherol showed possible antioxidant properties in the neurotoxicity evaluation resulting in higher cell viability. Even though liposomes illustrated higher efficacy and little haemolysis and ROS production, no difference in neurotoxicity was observed together with unfavourable properties during stability testing makes this drug delivery system less favourable in comparison to Pheroid™ vesicles. Mefloquine was successfully incorporated into Pheroid™ vesicles resulted in high efficacy and showed possible neuroprotection and therefore makes it an ideal system for treatment of malaria.Thesis (Ph.D. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2011
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Jarzębińska, Anita [Verfasser], and Ernst [Akademischer Betreuer] Wagner. "Lipid-based delivery system for chemically modified mRNA / Anita Jarzębińska ; Betreuer: Ernst Wagner." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2017. http://d-nb.info/1136270884/34.
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Brody, Leigh. "Design, synthesis and biological evaluation of novel lipid-based nanoparticle delivery system for metabolic re-engineering." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/14406.
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Dietary supplementation with fibre has been shown to ameliorate features of the metabolic syndrome and inhibit malignant growth in certain types of cancer. These effects have been linked to short-chain fatty acids (SCFA), mostly acetate. However, the ubiquitous role of SCFAs in metabolism, combined with a short tissue half-life and the non-targeted nature of oral and peripheral administrations make achieving phenotypically relevant levels of SCFA by standard delivery techniques challenging and limit their therapeutic potential. Liposomal encapsulation of a therapeutic agent overcomes these issues by protecting against degradation, increasing circulation time and passively targeting both the liver and tumour tissue. In this research project, I have designed a bifunctional liposome formulation to transport SCFA, monitored their distribution and uptake utilising visualisation by MRI, PET/CT and fluorescence microscopy. These bifunctional liposomes were useful for effectively encapsulating small molecules within their aqueous core, which in this case was acetate, and capable of acetate delivery into cells while also being amenable to cellular imaging. I have shown that preferential delivery of liposome encapsulated acetate (LITA) nanoparticles to key sites of metabolic control provide beneficial therapeutic effects in animal models of both obesity and cancer. Chronic administration of LITA nanoparticles in an obeseogenic model led to a significant reduction in adiposity, intrahepatocellular lipid, inflammatory tone and genetic indication of a decrease fatty acid synthesis in the liver. Application of LITA in a murine xenograft model caused an inhibition of tumour growth in three colorectal cancer cell lines: HT-29, HCT116 p53+/+ and HCT116 p53-/-. The mechanisms for these two outcomes are not fully defined; however cellular energy homeostasis of both scenarios was restored. These results indicate that LITA nanoparticles can be used to improve multiple metabolic pathways, in vivo.
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Schwab, Martin. "Degradation of lipid based drug delivery systems and characterization of semi-synthetic spider silk proteins for the application in pharmaceutical technology." Diss., Ludwig-Maximilians-Universität München, 2009. http://nbn-resolving.de/urn:nbn:de:bvb:19-165238.
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Gujrati, Maneesh. "Development of a Multifunctional Cationic Lipid-Based siRNA Delivery System for the Treatment of Triple-Negative Breast Cancer." Case Western Reserve University School of Graduate Studies / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1432742230.
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Song, Lin. "STUDIES OF SOLUBILIZATION OF POORLY WATER-SOLUBLE DRUGS DURING IN VITRO LIPOLYSIS OF A MODEL LIPID-BASED DRUG DELIVERY SYSTEM AND IN MIXED MICELLES." UKnowledge, 2011. http://uknowledge.uky.edu/pharmacy_etds/1.
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Lipid-based drug delivery systems (LBDDSs) are becoming an increasingly popular approach to improve the oral absorption of poorly-water soluble drugs. Several possible mechanisms have been proposed to explain the means by which LBDDSs act in vivo to enhance absorption. The goal of the current dissertation is to provide a better understanding of one proposed mechanism; the capability of lipoidal components in LBDDS formulations to create and maintain a drug in a supersaturated state under simulated GI conditions. Moreover, molecular details of equilibrium solubilization of a drug in a series of model lipid assemblies were examined. The results of these studies will aid formulators in choosing the optimal LBDDS to improve oral absorption of poorly water-soluble drugs.
Time-dependent solubilization behavior of progesterone, 17β-estradiol and nifedipine in a simple model LBDDS composed of Polysorbate 80 was assessed employing the in vitro dynamic lipolysis model. The results illustrated the extent to which the supersaturated state was dependent on the extent of lipolysis of Polysorbate 80 and the initial drug concentration. Area-under-the curve-supersaturation was proposed as a means of quantifying the time-dependent extent of supersaturation in LBDDSs in simulated intestinal conditions.
Concurrently, a series of model mixed micellar solutions, composed of Polysorbate 80 and oleic acid, were prepared to represent the lipid assemblies produced during the lipolysis experiments. The ability of these aggregates to solubilize progesterone, 17β-estradiol and nifedipine were evaluated and the aggregate/water partition coefficients were determined. The Treinor model was found to successfully fit the partition coefficients of the drugs in a range of mixed micelles. The equilibrium solubility of drugs in the mixed micelles was calculated and compared to that found under lipolytic conditions. The best agreement between calculated and experimental conditions was observed for nifedipine. These studies have established a foundation for the evaluation of time-dependent extent of supersaturation with more complex LBDDS formulations exposed to lipolytic conditions.
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Schwab, Martin [Verfasser], and Gerhard [Akademischer Betreuer] Winter. "Degradation of lipid based drug delivery systems and characterization of semi-synthetic spider silk proteins for the application in pharmaceutical technology / Martin Schwab. Betreuer: Gerhard Winter." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2014. http://d-nb.info/1046785257/34.
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Klein, Sandra Verfasser], Karsten [Akademischer Betreuer] [Mäder, Markus [Akademischer Betreuer] Pietzsch, and Thomas [Akademischer Betreuer] Rades. "In vitro lipolysis assay as a prognostic tool for the development of lipid based drug delivery systems / Sandra Klein. Betreuer: Karsten Mäder ; Markus Pietzsch ; Thomas Rades." Halle, Saale : Universitäts- und Landesbibliothek Sachsen-Anhalt, 2013. http://d-nb.info/1031189815/34.
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Carradori, Dario. "Novel nanoparticle-based drug delivery system for neural stem cell targeting and differentiation." Thesis, Angers, 2017. http://www.theses.fr/2017ANGE0056/document.
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Les cellules souches neurales (CSNs) se situent dans des régions spécifiques du système nerveux central qui sont appelées niches. Ces cellules sont capables de se répliquer ou se différentier en cellules neurales spécialisées (neurones, astrocytes et oligodendrocytes). C’est grâce à cette propriété de différentiation que les CSNs sont étudiées comme thérapie chez les patients atteints d’une maladie neurodégénérative. En effet, elles pourraient remplacer les cellules neurales altérées et ainsi restaurer les fonctions neurologiques. De nombreuses approches ont été développées afin de stimuler la différentiation des CSNs, dont la plus prometteuse est la différentiation des cellules endogènes directement au sein de leurs niches. Actuellement, il n’existe pas de molécule active ou de système thérapeutique qui cible les CSNs endogènes et qui induit leur différentiation simultanément. Le but de ce travail est de fournir un système de délivrance de molécules bioactives capable de cibler les CSNs endogènes et d'induire leur différenciation in situ. Nous avons développé et caractérisé des nanoparticules lipidiques (LNC), un système de délivrance très versatile. NFL-TBS.40-63, un peptide ciblant les CSNs, a été adsorbé à la surface des LNC afin de les diriger contre les CSNs endogènes. Nous avons observé que ces NFL-LNC ne ciblaient que les CSNs du cerveau et pas de la moelle. Afin d’étudier les interactions spécifiques entre les nanoparticules et les CSNs, nous avons caractérisé et comparé les propriétés de leur membrane plasmique. Enfin, nous avons encapsulé de l’acide rétinoïque, une molécule connue pour stimuler la différentiation des CSNs, dans les LNC-NFL et étudié leur impact sur la différentiation de CSNs in vitro et in vivo. Ce travail contribue au développement de thérapies efficaces et sures pour le traitement de maladies neurodégénératives à travers la différentiation de CSNs endogènesNeural stem cells (NSCs) are located in specific regions of the central nervous system called niches. Those cells are able to self-renew and to differentiate into specialized neuronal cells (neurons, astrocytes and oligodendrocytes). Due to this differentiation property, NSCs are studied to replace neuronal cells and restore neurological functions in patients affected by neurodegenerative diseases. Several therapeutic approaches have been developed and endogenous NSC stimulation is one of the most promising. Currently, there is no active molecule or therapeutic system targeting endogenous CSNs and inducing their differentiation at the same time. The aim of the work was to provide a drug delivery system able both to target endogenous CSNs and to induce their differentiation in situ. Here, we developed and characterized lipidic nanoparticles (LNC) targeting endogenous NSCs. A peptide called NFL-TBS.40-63, known for its affinity towards NSCs, was adsorbed at the surface of LNC. We observed that NFL-LNC specifically targeted NSC from the brain and not from the spinal cord in vitro and in vivo. To explain this specificity, we characterized and compared NFL-LNC interactions with the plasmatic membrane of both cell types. Finally, we demonstrated that by loading retinoic acid in NFL-LNC we were able to induce brain NSC differentiation in vitro and in vivo. This work contributes to the development of efficient and safe therapies for the treatment of neurodegenerative disease via the differentiation of endogenous NSCs
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Cao, Yichen. "APPLICATION OF LINEAR FREE ENERGY RELATIONSHIPS IN THE PREDICTION OF TRIGLYCERIDE/WATER PARTITION COEFFICIENTS AND LIPID BILAYER PERMEABILITY COEFFICIENTS OF SMALL ORGANIC MOLECULES AND PEPTIDES." UKnowledge, 2008. http://uknowledge.uky.edu/gradschool_diss/655.
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Computational methods such as linear free energy relationships (LFERs) offer a useful high-throughput solution to quickly evaluate drug developability, e.g. membrane permeability, organic solvent/water partition coefficients, and solubility. LFERs typically assume the contribution of structural components/functional groups to the overall properties of a given molecule to be constant and independent. This dissertation describes a series of studies in which linear free energy relationships were developed to predict solvation of small organic molecules in lipid formulations, specifically, triglyceride containing solvents and phospholipid-based liposomes. The formation of intermolecular HBs in triglyceride solvents (homogenous with H-bond accepting ability) and intramolecular HBs within the bilayer barrier domain (hydrocarbon-like) proved to be the major factors to consider in developing LFERs to account for the increased oil/water partition coefficients and enhanced bilayer permeability of small organic molecules.
The triglyceride solvent/water partition coefficients of a series of model compounds varying in polarity and H-bond donating/accepting capability were used to establish a correlation between the solvent descriptors and the ester concentration in these solvents using the Abraham LFER approach. The LFER analyses showed that the descriptors representing the polarizability and H-bond basicity of the solvents vary systematically with the ester concentration.
A fragment-based LFER to predict membrane permeability or 1,9- decadiene/water partition coefficients of small organic molecules including small peptides was systematically constructed using a total of 47 compounds. Significant nonadditivity was observed in peptides in that the contribution of the peptide backbone amide to the apparent transfer free energy from water into the bilayer barrier domain is considerably smaller than that of a “well-isolated” amide and greatly affected by adjacent polar substituents on the C-termini.
In order to explain the phenomenon of nonadditivity, the formation of intramolecular HBs and inductive effects of neighboring polar groups on backbone amide, were investigated using FTIR and MD simulations. Both spectroscopic and computational results provided supportive evidence for the hypothesis that the formation of intramolecular HBs in peptides is the main reason for the observed nonadditivity of Δ(ΔG°)-CONH-. The MD simulation results showed that the inductive effect of neighboring groups is not as important as the effect of intramolecular HBs.
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Myschik, Julia, and n/a. "Immunostimulatory lipid implants as delivery systems for model antigen." University of Otago. School of Pharmacy, 2008. http://adt.otago.ac.nz./public/adt-NZDU20080806.114447.
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Aim: Subunit vaccines have received increasing attention due to their good safety profile. However, subunit vaccines feature low immunogenicity, and soluble antigen is largely ignored by the immune system due to its lack of danger signals. To stimulate an appropriate immune response, subunit antigen vaccines require the addition of an adjuvant and multiple administrations. This study aimed to formulate biodegradable lipid implants, containing a suitable adjuvant, which delivers antigen in a sustained manner. The physico-chemical characteristics of the implants and their ability to stimulate immune responses towards a model antigen in vivo were investigated.
Methods: Lipid implants were prepared from phospholipid and cholesterol. Different adjuvants were added, and their potential to induce an immune response to the model antigen ovalbumin (OVA) was investigated. The adjuvants and immunomodulators assessed were Quil-A (QA), imiquimod, and an α-Galactosylceramide (α-GalCer) analogue. Liposomal dispersions were prepared using the lipid film hydration method. These were freeze-dried, and the powder compressed into matrices (diameter of 2 mm). Physico-chemical characterisation was undertaken by transmission electron microscopy (TEM) to investigate the release of colloidal structures (liposomes, immunostimulating complexes [ISCOMs]) upon hydration with release media. Surface changes of the implant matrices were analysed using scanning electron microscopy (SEM). The release of the fluorescently-labelled antigen ovalbumin (FITC-OVA) and its entrapment into the colloidal particles was investigated using spectrofluorophotometry. Additionally, incorporation of the cationic cholesterol derivative DC-cholesterol (DCCHOL) into implants to allow for charge-charge interactions with the negatively-charged OVA, and replacement of the phospholipid with a phospholipid having a higher transition temperature to facilitate the manufacturing process, were attempted and assessed. The immune response stimulated towards OVA released from the implants was analysed in vivo using a C57Bl/6 mouse model. Expansion of CD8⁺ T cells and CD8 T cells specific for the CD8 epitope of OVA (SIINFEKL), as well as expansion of CD4⁺ T cells, were assessed. The ability of implants to stimulate T cell proliferation and interferon-γ production after in vitro restimulation with OVA was analysed. Serum samples were analysed for OVA-specific IgG antibodies.
Results: Lipid implants containing Quil-A released colloidal structures upon hydration with buffer. The type of colloids observed by TEM depended on the ratio of QA:cholesterol:phospholipid. Release of OVA was sustained over ten days in implants prepared with egg yolk PC. However, the release kinetics depended strongly on the choice of phospholipid. In vivo, lipid implants containing Quil-A evoked expansion of CD8⁺ T cells. The immune response to one implant was comparable to that obtained by two equivalent injection immunisations. Therefore, the implants obviated the need for multiple immunisations in the vaccination regime tested here. Expansion of CD8⁺ T cells towards the Quil-A-containing implant was greater than that achieved by the immunomodulators imiquimod and the α-GalCer analogue. Quil-A-containing implants produced OVA-specific IgG antibodies to a greater extent than the implants containing imiquimod or α-GalCer. Incorporation of the cationic DCCHOL did not increase the entrapment efficiency of OVA into liposomes. However, the in vivo investigation of DCCHOL-containirig implants showed an adjuvant effect of DCCHOL on antibody responses, but not on cell-mediated immunity.
Conclusion: Lipid implants offer great potential as sustained release vaccine delivery systems. The lipid components in the implant formulation were well-tolerated and biodegradable. Lipid implants combine the advantages of sustained release of antigen and particulate delivery by the formation of colloidal particles.
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Zhang, Mengzi. "DEVELOPMENTS OF LIPID-BASED NANOPARTICLES FOR THERAPEUTIC DRUG DELIVERY." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1417025932.
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Al, Sukhun Rajaa Abed El-Kader. "Lipid drug delivery systems and their fate after oral administration." Thesis, University of Bath, 2002. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.665369.
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A novel class of lipid formulation was investigated comprising GRAS (generally regarded as safe) materials. The formulations were all ‘surfactant-free’ (S-F) formulations, and also referred to as ‘Type IV’ lipid formulations. These formulations were isotropic, transparent, thermodynamically stable at room temperature and typically composed of > 50 % of mixed mono-, di- and triglycerides, > 30 % medium chain fatty acids oil and < 20 % hydrophilic co-solvent. At equilibrium, S-F formulations enhanced the solvent capacity of corticosteroids (log P > 3) and hydroxy benzoate derivatives over type II SEDDS and type III SEDDS, but generally were not superior solvents to mixtures of mono-, di- and triglycerides (Imwitor 988® and or Capmul MCM®) alone, for lipophilic steroids (log P < 3). In general, type III SEDDS which were composed of high hydrophilic content (hydrophilic surfactant, HLB > 1 2 , and hydrophilic co-solvent), were also better solvents for most steroidal compounds and hydroxy benzoate derivatives than type II SEDDS and type I SEDDS formulations. Surfactant with HLB > 12 inhibited lipolysis of MCT and mixed glycerides when the concentration of surfactant exceeded 40 % w/w. Hydrophobic surfactants (HLB < 10) did not inhibit lipolysis. Thus, the digestibility of dispersions formed by selfemulsifying systems would be dependent on the surfactants used and the quantity of TG available for lipolysis. Co-solvents did not appear to influence lipolysis, once the formulations had dispersed. Phase separation of lipid formulations following their dispersion in simulated intestinal fluid was studied. The lipid formulation behaviour was dependent on monoglyceride content. When sufficient monoglyceride (> 60 %w/v) was present demulsification and phase separation was noticed and was found to be dependent on the presence of phospholipid. This resulted in sedimentation of the phase rich V monoglyceride and water. The presence of triglyceride stabilised the formation of mixed micelles, which remained in a finely dispersed state. This unexpected phase separation is likely to have a considerable effect on the fate of drug dissolved in SEDDS formulations. The high concentrations of monoglyceride may be disadvantageous and could possibly result in precipitation of drug.
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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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Liu, Weipeng. "Biopolymer-based ocular drug delivery systems." Diss., Connect to online resource - MSU authorized users, 2008.
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Mohamed, Noor Norhayati. "Lipid-based nanoparticles for topical delivery of hair growth therapeutic molecules." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/10024622/.
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INTRODUCTION: Androgenic alopecia (AA) patients usually have high levels of dihydrotestosterone on their balding scalp area. Currently, dutasteride (DST) is given orally and has systemic adverse effects; diminished sexual desire, increased depression and ejaculation disorder. Topical administration of DST is an appropriate drug-delivery strategy with the potential to reduce systemic side effect, skin irritation and cytotoxicity effects. MATERIALS AND METHOD: Chitosan oligomer (CSO) conjugated with stearic acid (SA) or lauric acid (LA) was synthesised and characterised. Dutasteride-loaded nanostructured lipid carriers (DST-NLCs) were prepared using a melt-dispersion ultrasonication method. DST-NLCs were optimised using a design of experiments approach. DST-NLCs, uncoated and coated with CSO-SA or CSO-LA were characterised for particle size distribution, surface charge and morphology. In vitro release and permeation studies were performed. Cytotoxicity was investigated using human hair follicle dermal papilla cells, and skin irritation was performed using an EpiDermTM RHE model. Cou-6 loaded NLCs were prepared and characterised before proceeding with the cell and skin uptake study. RESULTS: CSO-SA and CSO-LA were successfully synthesised; confirmed using 1H NMR and FTIR. The mean size of DST-NLCs was significantly increased (p < 0.05) when coated with 5% CSO-SA but not with 5% CSO-LA (p > 0.05). The zeta potential changed from negative to positive charge when coating DST-NLCs with CSO-SA or CSO-LA. All formulations were physically stable over six months when stored at 4-8°C. However, DST-NLCs coated with CSO showed aggregation. All formulations exhibited rapid drug release. No dutasteride permeated through pig ear skin after 48 h for all formulations. The cytotoxicity (IC50) for DST nanoparticles, coated and uncoated, was greater than for DST alone (p < 0.05). The in vitro skin irritation study indicated no irritation for all nanoparticle preparations. For the cell and skin uptake studies, all samples showed time-dependent skin and cell uptake. CONCLUSIONS: These stable, low cytotoxic and irritant, positively-charged DST-NLCs with CSO-SA or CSO-LA, represents a promising strategy for topical/ transfollicular delivery of DST.
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Solomon, Linda Joy. "Lipid-based formulations for oral delivery of poorly water-soluble drugs." Thesis, University of Bath, 1998. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263231.
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Triplett, Michael David. "Enabling solid lipid nanoparticle drug delivery technology by investigating improved production techniques." Connect to this title online, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1101830018.
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Thesis (Ph. D.)--Ohio State University, 2004.Title from first page of PDF file. Document formatted into pages; contains xv, 172 p.; also includes graphics (some col.). Includes bibliographical references (p. 161-172).
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Cheng, Xinwei. "Development of a Lipid Nanoparticle-based Antisense Delivery Platform for Cancer Therapy." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu154323360801958.
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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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Webster, Alexandra Margaret. "Design, synthesis and delivery of peptide-based systems." Thesis, Durham University, 2018. http://etheses.dur.ac.uk/12616/.
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Peptide-based therapeutics have been an active area of research for a number of years. They have been found applications as drug-delivery agents, anticancer therapies and as antibiotics, the latter of which is particularly notable when set against a present-day backdrop of the increasing problem of antibiotic resistance. However, the use of peptides is still limited as they suffer from poor bioavailability as a result of their vulnerability to proteolytic degradation. Peptoids are a class of peptidomimetics which represent a potential proteolytically stable alternative to peptides. Chapter 1 introduces peptoids, common methods of their synthesis and their potential therapeutic applications. The challenges associated with controlling peptoid secondary structure are also discussed, along with commonly seen methods of imposing conformational rigidity. Chapter 2 details our attempts to address this problem by synthesising a library of biaryl-containing cyclic peptoids which represent novel peptoid scaffolds. In Chapter 3, we synthesise the active domain (p15) of the known anticancer peptide CIGB-300 along with three stapled analogues on which binding assays can be carried out. In Chapter 4, we synthesise six cell-penetrating peptoids (CPPos) which have previously been reported to localise in mitochondria. Onto these peptoids we conjugated the known anticancer peptide D-KLA and show the ability of these peptoids to increase proapoptotic activity. Flow cytometry and confocal microscopy is then used to demonstrate mitochondrial localisation of the most active peptide-peptoid hybrid, KLA-CPPo6. Having shown the ability of CPPos to transport biologically active cargo, we then conjugate the p15 peptide, previously introduced in Chapter 3, to the six CPPos in preparation for the evaluation of their anticancer activity.
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Mackenzie, R. C. "Computational modelling of polymer-based drug delivery systems." Thesis, University of Nottingham, 2015. http://eprints.nottingham.ac.uk/28852/.
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Polymer-based drug delivery systems have fantastic potential in chemotherapy as they can reduce drug side effects, help in patient compliance and provide targeting. Nanoprecipitation is used to encapsulate small drug molecules into polymer nanoparticles to form a drug delivery system. A major obstacle in polymer-based drug delivery systems reaching the clinic is their inability to load sufficient drug molecules. Little is known about the processes involved in the encapsulation of drug molecules into these delivery systems. An insight into the processes that govern the formation of these particles and encapsulation of small drug molecules within them is therefore desirable. We used molecular dynamics to model nanoprecipitation by simulating the dispersion of an acetone drop, containing polymer, into water containing drug. To allow sufficient dispersion of acetone a large amount of water is required, thus coarse-graining becomes mandatory. However, we maintain accuracy for our polymer-drug interactions by using a multiscale force field. Atomistic polymer and drug molecules contain coarse-grain virtual sites which facilitate interactions with the coarse-grain solvent molecules. We also employed fully atomistic reference simulations via resolution transformation to optimise our multiscale force field. This thesis details the theory and design behind this model of nanoprecipitation including how other techniques produced inferior results. Initial simulations with our multiscale model matched an experimental trend and were shown to be accurate relative to atomistic reference simulations. We also analysed a fully atomistic simulation of nanoprecipitation that took several months to complete. This atomistic simulation was used as a reference to update the multiscale force field. The updated force field improved on some aspects of the simulation but there are still areas that need improvement. Insight from the simulations provides an understanding of the experimental results and trends. The transferability of the model should help in designing more efficient polymer-based drug delivery systems in the future. We conclude with future work on modelling polymer-based drug delivery systems including alternate methods to gain understanding of not only drug incorporation but also drug release.
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Guiheneuf, Thierry Michel Herve. "Magnetic resonance imaging of meat- and lipid-based food systems." Thesis, University of Cambridge, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627488.
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Deng, Ni. "A secure, payment-based email delivery system." CSUSB ScholarWorks, 2005. https://scholarworks.lib.csusb.edu/etd-project/2909.
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Oh, Sejin. "Development of mucus permeating nanoparticles-based drug delivery systems." Doctoral thesis, Universitat Ramon Llull, 2016. http://hdl.handle.net/10803/382626.
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Existeix un interès creixent, tant en el món acadèmic com en la recerca industrial en el desenvolupament de sistemes d’alliberament de fàrmacs macromoleculars (proteïnes, pèptids, oligonucleotids) capaços de travessar la mucosa. En aquest sentit, la utilització de vectors sintètics per a l’alliberament de les esmentades macromolècules, permet disposar d’una plataforma versàtil i altament eficient. Tanmateix, la capa de mucosa amb propietats adhesives i altament viscoelàstica, té una elevada capacitat d’atrapar i eliminar qualsevol substància estranya que quedi adherida sobre la seva superfície, limitant, de forma evident, la eficàcia de qualsevol tractament
Aquesta Tesi es centra en el desenvolupament de sistemes d’alliberament de DNA, dissenyats a mida, que presenten una elevada estabilitat i eficàcia de transfecció amb un nivell molt baix de toxicitat i molt important en el context de la tesi, una capacitat de permeació a través de la mucosa. A més la tesi també es centra en el disseny i el desenvolupament de mètodes i tècniques in vitro que ajudin a una millor selecció de sistemes eficients d’alliberament a través de la mucosa.
Així s’ha desenvolupat un mètode simple i eficient, basat en la utilització de una microbalança de quartz amb dissipació (QCM-D). Aquest mètode ha permès avaluar la interacció de polímers i nanopartícules amb una capa de mucina. Els resultats obtinguts amb el mètode desenvolupat han permés dissenyar sistemes de nanopartícules amb un potencial més gran de permeació a través de la mucosa. Aquesta tècnica d’alta sensibilitat també ha ofert la possibilitat d’avaluar las dos propietats oposades, el coneixement de les quals és necessari per un correcte disseny de sistemes cpaços de creuar la mucosa: mucoadhesió vs mucopenetració.
Los Poly(β-amino ester)s (PBAEs) s’han proposat com a sistemes biodegradables capaços de formar nanopartícules, per complexació amb DNA, que presenten una elevada capacitat de transfecció. Tanmateix, mostren problemes d’estabilitat en condicions fisiològiques i són incapaços de travessar la capa de mucosa. En aquesta tesi es descriu una nova solució en la preparació de les formulacions dels nanocomplejos basada en la utilització de recobriments que estabilitzen les nanopartícules i augmenten la seva permeabilitat. Els recubrimeintos proposats inclutyen: i) sucres (sucroses, trhalosa i manitol), ii) quitosà sense modificar de 22 KDa i amb 60-120 kDa, iii) quitosan modificat amb àcid tioglicolidoi i iv) acid poliacrílic-bromelaina. Totes les noves formulacions s’han avaluat amb diferents quantitat de recobriment. S’han determinat les seves propietats fisicoquímiques i la seva eficàcia de transfecció i citotoxicitat en front de cèl.lules COS-7. S’ha estudiat La difusió de las partícules a través de la mucosa gàstrica de porc utilitzant diferents tècniques com el tub rotatori de silicona o el multiple particle tracking (MPT).
Els resultats obtinguts han mostrat la superior estabilitat, eficàcia de transfecció i permeabilitat sobre la mucosa de las noves formulacions dissenyades.Existe un interés creciente, tanto en el mundo académico como en la investigación industrial en el desarrollo de sistemas de liberación de fármacos macromoleculares (proteínas, péptidos, oligonucleótidos) capaces de atravesar la mucosa. En este sentido, la utilización de vectores sintéticos para la liberación de dichas macromoléculas, permite disponer de una plataforma versátil y altamente eficiente. Sin embargo, la capa de mucosa con propiedades adhesivas y altamente viscoelástica, tiene una elevada capacidad de atrapar y eliminar cualquier sustancia extraña que quede adherida sobre su superficie, limitando, de forma evidente, la eficacia de cualquier tratamiento Esta Tesis se centra en el desarrollo de sistemas de liberación de ADN, diseñados a medida, que presentan una elevada estabilidad y eficacia de transfección con un nivel muy bajo de toxicidad y muy importante en el contexto de la tesis, una capacidad de permeación a través de la mucosa. Además la tesis también se centra en el diseño y el desarrollo de métodos y técnicas in vitro que ayuden a una mejor selección de sistemas eficientes de liberación a través de la mucosa. Así se ha desarrollado un método simple y eficiente, basado en la utilización de una microbalanza de cuarzo con disipación (QCM-D). Este método ha permitido evaluar la interacción de polímeros y nanopartículas con una capa de mucina. Los resultados obtenidos con el método desarrollado han permitido diseñar sistemas de nanopartículas con un mayor potencial de permeación a través de la mucosa. Esta técnica de alta sensibilidad también ha ofrecido la posibilidad de evaluar las dos propiedades opuestas, el conocimiento de las cuales es necesario para un correcto diseño de sistemas cpaços de cruzar la mucosa: mucoadhesió vs mucopenetració. Los Poly (β-amino ester)s (PBAEs) se han propuesto como sistemas biodegradables capaces de formar nanopartículas, por complejación con ADN, que presentan una elevada capacidad de transfección. Sin embargo, muestran problemas de estabilidad en condiciones fisiológicas y son incapaces de atravesar la capa de mucosa. En esta tesis se describe una nueva solución en la preparación de las formulaciones de los nanocomplejos basada en la utilización de recubrimientos que estabilizan las nanopartículas y aumentan su permeabilidad. Los recubrimeintos propuestos inclutyen: i) azúcares (sucrosa, trhalosa y manitol), ii) quitosano sin modificar de 22 KDa y con 60-120 kDa, iii) quitosano modificado con ácido tioglicólico y iv) ácido poliacrílico-bromelaina. Todas las nuevas formulaciones se han evaluado con diferentes cantidades de recubrimiento. Se han determinado sus propiedades fisicoquímicas y su eficacia de transfección y citotoxicidad frente a células COS-7. Se ha estudiado La difusión de las partículas a través de la mucosa gástrica de cerdo utilizando diferentes técnicas como el tubo rotatorio de silicona o el múltiple particle tracking (MPT). Los resultados obtenidos han mostrado superior estabilidad, eficacia de transfección y permeabilidad sobre la mucosa de las nuevas formulaciones diseñadas.
Mucus penetrating nanoparticle-based delivery systems of macromolecular drugs are currently receiving increasing attention in both academic and industrial research. Synthetic delivery systems provide highly suitable and tunable platform for the delivery of the macromolecules. However, a highly viscoelastic and adhesive mucus layer generally traps and rapidly removes most foreign substance from the mucosal surfaces, thereby limiting effectiveness of these nanocarriers. This Thesis is addressed to the development of engineering DNA delivery systems capable of high stability and transfection efficiency with low toxicity, and quickly crossing the mucus layer. Moreover, this Thesis is focused on design and development of methods and techniques in vitro in order to select more efficient delivery systems. A simple and efficient method, based on the use of the quartz crystal microbalance with dissipation (QCM-D) technique, is developed and evaluated the interaction of the polymers and nanoparticles with the mucin layer, resulting in the development of nanoparticle-based delivery systems to mucosal tissue. This highly sensitive technique also offers to evaluate the two opposing properties, needed for the design of efficient mucous permeation systems: mucoadhesion vs mucus penetration. Poly(β-amino ester)s (PBAEs) are currently considered of great interest as biodegradable polymeric carriers of DNA delivery, but they present limited stability in physiological conditions and the inability to penetrate the mucus layer. In this Thesis, we describe a novel surface-modified formulation of DNA delivery systems consisting of PBAE/DNA complexes and the coating agents, including: i) sugars (sucrose, trehalose or mannitol), ii) unmodified chitosan with a 22 kDa (CS) and a with a 60-120 kDa (CSM), iii) chitosan-thioglycolic acid (CS-TGA), and iv) poly(acrylic acid)-bromelain (PAA-BRO) conjugates. All novel formulations formed with different amounts of the coating agents are evaluated the physicochemical properties. The influence of coating agents on transfection efficiency and cytotoxicity is evaluated in COS-7 cells. Particle diffusion through porcine intestinal mucus (PImucus) is assessed by either rotating silicone tube technique or multiple particle tracking (MPT). The results highlight the superior stability, transfection efficiency and mucus permeability of the novel nanoparticle-based drug delivery systems. The effect of the amount of coating agents is also discussed.
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Dua, Pinky. "Model based and parametric control for drug delivery systems." Thesis, Imperial College London, 2005. http://hdl.handle.net/10044/1/8040.
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Dixon, John Robert. "Examining the impacts of Web-based education delivery systems." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ58335.pdf.
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Schultze, Jennifer [Verfasser]. "Polymer-Based Systems for Drug Delivery Studies / Jennifer Schultze." Mainz : Universitätsbibliothek Mainz, 2019. http://d-nb.info/1186179627/34.
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Elahrash, K. S. "Some physical studies with polymer based drug delivery systems." Thesis, University of Brighton, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.354875.
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Mohd, Azmi Mohd Azraie Bin. "Integrated silicon nanowire biosensor and MEMS based delivery systems." Thesis, Swansea University, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.678641.
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Abodinar, Atiga Emhemed. "Construction of potential drug delivery systems based on polysaccharides." Thesis, University of Huddersfield, 2016. http://eprints.hud.ac.uk/id/eprint/32608/.
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Enhancement of the drug efficacy and elimination of the side effects resulting from drug overdoses are an essential aspect in drug therapy. To achieve these demands two general guidelines have been used; producing new drugs with higher selectivity and therefore less side effects and improving controlled/sustained drug delivery agents based on polymers. Thus, the relationship between the active pharmaceutical ingredient and the polymeric system is important in the development of a drug delivery system and several considerations need to be taken in to account, for example the polymer should be biocompatible, biodegradable, and non-toxic and physiochemical properties. Because mucus is the first barrier with which food and drugs can interact with and diffuse through to be absorbed and enter the circulatory system, characterisation of mucin is an essential step towards establishing suitable pharmaceutical excipients. Therefore, the aim of the present study was to investigate the potential to construct and study drug delivery systems based on polysaccharides. The physicochemical characterisation of extensively degraded pig gastric mucin was studied and revealed that this type of mucin contains: protein, carbohydrate (Fuc, Gal, GalN, GlcN) and sialic acid, which provides the negative charges that becomes progressively stronger with increasing pH. The measurements of viscosity vs. shear rate showed that mucin has a shear thinning behaviour and a relatively low viscosity which is consistent with a high critical overlap concentration (c*), small hydrodynamic size and hence compact structure. The insight in to the compositional, hydrodynamic and viscoelastic properties support the understanding of mucin interactions with polysaccharide based drug delivery systems. Several polysaccharides including chitosan (Cs), two grade of alginates; high guluronate alginate (HGA) and low guluronate alginate (LGA) (which differ in structural conformation) and two kinds of pectin; high methoxyl pectin (HMP) and low methoxyl pectin (LMP) (with different degrees of esterification) have been characterised. The structure of these polysaccharides as powder have been studied; Fourier transform infrared spectroscopy ) findings indicate the structure and the function group for each polysaccharide whereas powder X-ray diffraction measurements displays that all the polysaccharide which were analysed are amorphous in nature except LMP which has a number of sharp crystalline peaks. In addition, solution properties of these polysaccharides such as zeta potential and intrinsic viscosity were investigated at several ionic strengths and pH. Furthermore the molecular weights were evaluated based on intrinsic viscosity and the Smidsrød-Haug stiffness parameter (B) and intrinsic persistence length (Lp) were estimated using the novel ionic strength dependency of zeta potential method and intrinsic viscosity (traditional method). The interaction between polysaccharides and pig gastric mucin were evaluated based on relative viscosity. It has been suggested that polysaccharide–mucin interactions are not only driven by electrostatic forces, but also by the molecular weight, conformation and flexibility of the polymer also played significant roles. As the mucin-HGA system displayed exceptionally high viscosity, the viscoelastic properties of this system were extensively studied. The mechanical spectra of the mucin-HGA blends indicate that with the exception of the system involving only HGA (0 % mucin) and 60 % mucin, all mixtures including mucin itself displayed typical ‘weak gel’ rheological behaviour and the gel became stronger with decreasing HGA content in the system. Moreover 80 % of mucin was successfully encapsulated within phospholipids bilayer using liposomal encapsulation technology. The liposomal vesicles with encapsulated mucin display larger sizes than the control vesicles (prepared in DI water) this may be due to the electrostatic interaction between mucin molecules and phospholipid which is the main component the vesicles. In the final part of the thesis the hydrogel containing chitosan and naturally occurring polyanions and its potential for drug release were studied. Chitosan - polyanion (HGA, LGA, HMP and LMP) hydrogels complexes were successfully prepared (in acetate buffer 0.05M, 4.3 pH) at various ratios (10 %, 30 %, 50 %, 70 % 90 % of Cs) using the ionotropic gelation method. The freeze dried hydrogels were characterized by FT-IR and XRD and the results confirmed the electrostatic interactions between chitosan and polyanions at all ratios and percentage yield of hydrogel ζ and ηsp results of the supernatant was determined and it was found that the optimum ratios 3:7 and 1:1 of chitosan-pectins and chitosan-alginates respectively. The hydrogels of ideal ratios were studied by determining zeta potential, particles size, water uptake, morphology by scanning electron microscopy for freeze dried hydrogels and optical microscopy analysis for homogenous suspension. In addition, dynamic small deformation oscillatory measurements and adhesion property were studied. Finally, ibuprofen was successfully encapsulated by the chitosan-polyanion hydrogel complexes and the encapsulation efficiency of the formulations was calculated. Finally the drug release behaviour of the formulations was in vitro assessed over the time. The findings demonstrated that HMP and LGA hydrogels displayed the highest percentage of retained ibuprofen followed by HGA and LMP. This could be attributed to the fibrous appearance small size of pores which may impedes movements of entrapped molecules.
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Tang, Qiong. "Multifunctional Natural Material-based Delivery Systems for Gene Therapy." University of Akron / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=akron1415382826.
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Chen, Ming [Verfasser], Alfred [Akademischer Betreuer] Fahr, and Gerrit L. [Akademischer Betreuer] Scherphof. "Skin Drug Delivery From Different Lipid Vesicular Systems / Ming Chen. Gutachter: Alfred Fahr ; Gerrit L. Scherphof." Jena : Thüringer Universitäts- und Landesbibliothek Jena, 2011. http://d-nb.info/1017078890/34.
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Grove, Mette. "Development and characterisation of lipid-based formulations for oral delivery of poorly soluble drug substances /." Cph. : The Danish University of Pharmaceutical Sciences, Department of Pharmaceutics and Analytical Chemistry, 2006. http://www.dfuni.dk/index.php/Mette_Grove/3071/0/.
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Bethune, Claudette R. "The role of drug-lipid interactions in biodistribution and therapeutic effects for drugs incorporated into liposomes /." Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/7954.
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Booth, Ronald L. "An Information Systems Project Delivery Methodology for Implementing Web-Based Program Management Systems." NSUWorks, 2003. http://nsuworks.nova.edu/gscis_etd/420.
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In this study the researcher applied an Information Systems Project Delivery Methodology (ISPDM) for implementing a Web-based Program Management System in an organization that did not have one. The problem investigated in this study was the difficulty encountered when organizations implement ISPDMs. The research questions were (1) what is the role of each of Roberts' et al. five factors in the implementation of an ISPDM? And (2) how effective is a Web-based program management system implemented using an ISPDM in meeting the participants desired outcomes? The general approach utilized to address the research questions was to describe the implementation of a Web-based program management ISPDM using a single descriptive case study. A survey, focus group, and usability testing were utilized at three different stages of the Web-based program management module's implementation.
In conducting this study research, multiple sources of data were collected to develop an in-depth description of the case as it developed. The open-ended survey was given at three different points, the beginning, the middle and the end of the ISPDM Web based program management module implementation. A focus group was conducted for planning evaluation to assess the participant's desired outcomes for the Web-based program management system. A focus group for in-process evaluation assessed the extent to which the Web-based program management module achieved the outcome measures. A focus group for summative evaluation determined whether or not the final product met the expectations of the users. In addition, a usability survey was conducted in conjunction with the in-process and summative evaluation focus groups.
The results of this study indicated the role of organizational transition when implementing a Web-based program management system using an ISPDM is to provide training, education, and communications. The role of functional management involvement/support during the implementation process is to provide resources and lead the process of adopting the new methodology. The role of the ISPDM during the transition stage is to communicate the change and to foster cultural integration, provide a framework for using the product, and to provide training. The role of the use of software development models in the implementation process is to provide guidelines, framework, metrics, and to lend credibility to the value of the methodology. The role of external support during the implementation process is to provide an industry-wide knowledge base, oversight, and an independent review of the new methodology.
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Stasko, Nathan Allan Schoenfisch Mark H. "Synthesis and characterization of dendrimer-based nitric oxide delivery systems." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2007. http://dc.lib.unc.edu/u?/etd,1421.
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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2007.Title from electronic title page (viewed Apr. 25, 2008). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Chemistry." Discipline: Chemistry; Department/School: Chemistry.
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Mistry, Ajay Ramanlal. "Development of non-viral gene delivery systems based on HMG1." Thesis, Imperial College London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368705.
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Bergin, Paul Michael. "Approaches to functionalised amine-based ligands for radiopharmaceutical delivery systems." Thesis, University of Southampton, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.409852.
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Iemsam-Arng, J. "Poly(ethylene) glycol based delivery systems for nucleic acid therapies." Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1381001/.
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Our work is aimed at developing a synthetic biocompatible gene and siRNA delivery system for the treatment of primary and metastatic tumours. To facilitate delivery of nucleic acid based drugs into the cell, one strategy is to formulate the naked gene with an amine based non-viral gene delivery system via the counterion interaction. The delivery systems including 4arm-PEG-amine, 4arm-PEG-N-2-ethylamine, 8arm-PEG-amine and 8arm-PEG-N-2-ethylamine were synthesised, characterised and complexed with a reporter gene (β-gal plasmid DNA) in phosphate buffer pH 6.0. The resulting complexes were sized and their zeta potential measured (Malvern Zetasizer 3000HS, Malvern Instruments, UK). The complexes were also imaged using transmission electron microscopy and characterised for DNA binding and DNA protection using gel electrophoresis and the ethidium bromide displacement assay. The in vitro transfection efficiency and cell cytotoxicity of the complexes were determined in the A431 and HeLa cells. Additionally, in vivo therapeutic studies in female nude tumour bearing mice were carried out. A promising DNA-polymer complex of 4arm-PEG-N-2-ethylamine produced a complex of 200-300 nm in diameter (polydispersity < 0.6). Complexes had a zeta potential of +19.8 mV (n=3) and were spherical, fibrillar and toroidal in shape. The new gene delivery complex protected DNA from degradation in serum up to 2 hours and was as efficient as poly(ethylenimine) (PEI) in transfecting the A431 cell line, but it was more than 3 orders of magnitude less cytotoxic than PEI. In vivo a gene medicine, comprising the polymer and the tumour necrosis factor alpha gene, was tumouricidal. When complexed with siRNA, the siRNA polymer complex demonstrated a trend of gene silencing activity. A new synthetic gene delivery polymer of 4arm-PEG-N-2-ethylamine has been synthesised. This polymer is biocompatible to cells and is an efficient in vitro and in vivo gene transfer agent.
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Culcuoglu, Mustafa U. "Reengineering Community Based Chronic Care Delivery Systems: Theory and Applications." University of Akron / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=akron1627573050496332.
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Oladiran, Gbolahan S. "Development and formulation of wax-based transdermal drug delivery systems." Thesis, Aston University, 2008. http://publications.aston.ac.uk/11060/.
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Topical and transdermal formulations are promising platforms for the delivery of drugs. A unit dose topical or transdermal drug delivery system that optimises the solubility of drugs within the vehicle provides a novel dosage form for efficacious delivery that also offers a simple manufacture technique is desirable. This study used Witepsol® H15 wax as a abase for the delivery system. One aspect of this project involved determination of the solubility of ibuprofen, flurbiprofen and naproxen in the was using microscopy, Higuchi release kinetics, HyperDSC and mathematical modelling techniques. Correlations between the results obtained via these techniques were noted with additional merits such as provision of valuable information on drug release kinetics and possible interactions between the drug and excipients. A second aspect of this project involved the incorporation of additional excipients: Tween 20 (T), Carbopol®971 (C) and menthol (M) to the wax formulation. On in vitro permeation through porcine skin, the preferred formulations were: ibuprofen (5% w/w) within Witepsol®H15 + 1% w/w T; flurbiprofen (10% w/w) within Witepsol®H15 + 1% w/w T; naproxen (5% w/w) within Witepsol®H15 + 1% w/w T + 1% C and sodium diclofenac (10% w/w) within Witepsol®H15 + 1% w/w T + 1% w/w T + 1% w/w C + 5% w/w M. Unit dose transdermal tablets containing ibuprofen and diclofenac were produced with improved flux compared to marketed products; Voltarol Emugel® demonstrated flux of 1.68x10-3 cm/h compared to 123 x 10-3 cm/h for the optimised product as detailed above; Ibugel Forte® demonstrated a permeation coefficient value of 7.65 x 10-3 cm/h compared to 8.69 x 10-3 cm/h for the optimised product as described above.
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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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Scally, David James. "Novel polyethylene glycol based drug delivery systems : a calorimetric and QASAR based study." Thesis, University of Kent, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.282425.
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