Um die anderen Arten von Veröffentlichungen zu diesem Thema anzuzeigen, folgen Sie diesem Link: Novel drug delivery system.
Dissertationen zum Thema „Novel drug delivery system“
Geben Sie eine Quelle nach APA, MLA, Chicago, Harvard und anderen Zitierweisen an
Machen Sie sich mit Top-50 Dissertationen für die Forschung zum Thema "Novel drug delivery system" bekannt.
Neben jedem Werk im Literaturverzeichnis ist die Option "Zur Bibliographie hinzufügen" verfügbar. Nutzen Sie sie, wird Ihre bibliographische Angabe des gewählten Werkes nach der nötigen Zitierweise (APA, MLA, Harvard, Chicago, Vancouver usw.) automatisch gestaltet.
Sie können auch den vollen Text der wissenschaftlichen Publikation im PDF-Format herunterladen und eine Online-Annotation der Arbeit lesen, wenn die relevanten Parameter in den Metadaten verfügbar sind.
Sehen Sie die Dissertationen für verschiedene Spezialgebieten durch und erstellen Sie Ihre Bibliographie auf korrekte Weise.
1
Blackwell, Lisa Jane. „Sporopollenin exines as a novel drug delivery system“. Thesis, University of Hull, 2007. http://hydra.hull.ac.uk/resources/hull:7162.
Der volle Inhalt der QuelleAnnotation:
Microcapsules are fast becoming the most successful delivery systems for the oral delivery of drugs and food additives. Since many drugs are proteins and are destroyed in acidic conditions, microcapsules offer protection against the harsh environment of the gastrointestinal (GI) tract. Although the use of microcapsules achieves controlled release of the inner material, many synthetically designed microcapsules lack consistency in their size and morphology. The outer coat (exine) of plant pollen grains and spores is composed of the material sporopollenin. Sporopollenin exines (25µm diameter) were extracted from Lycopodium clavatum and were investigated as a novel drug delivery system that was inexpensive, non-toxic, from a renewable source, and exhibited a large internal cavity for loading of hydrophobic and hydrophilic substances. They showed many advantages over conventional microcapsules, including their constant chemical structure and size within a species, and their ability to offer UV and air-oxidation protection. Previous studies have shown that particles such as pollen, spores and starch migrate into the bloodstream following ingestion by a process termed 'Persorption'. Such findings intrigued many researchers but the phenomenon has not been unanimously accepted. This research is a body of evidence giving unequivocal confirmation that spores of Lycopodium clavatum and their emptied exines were absorbed into the bloodstream of man to the same extent following oral ingestion, with a maximum of 10% (± 2%) of the dose recovered just 15-30 minutes after ingestion. These findings resolve the debate between researchers in support of persorption and those against, whom doubted the transport of particles of micron size into the bloodstream, but did not disprove such a phenomenon. An extensive study was undertaken to investigate the effect of factors such as gender, age, quantity and the method of ingestion on the rate and extent of exine absorption into the bloodstream. In a preliminary in vivo experiment the successful delivery of fish oil into the bloodstream via sporopollenin exines was illustrated. A major breakthrough has formed the foundations of this research. Although sporopollenin exhibits incredible stability to organIc and inorganic solvents, in contrast, this research has shown that exines degrade very rapidly in blood plasma both in vitro and in vivo. In vitro experiments were conducted in an attempt to characterise the specific mechanism responsible for exine degradation. Progression of work has provided much evidence that the conversion of plasminogen to the enzyme plasmin is either partially or wholly responsible for the characteristic degradation of sporopollenin in the blood. Further investigations showed that it was possible to load a sufficient quantity of substances into sporopollenin exines, such as human growth hormone (hGH) , Enfurvitide (an antiretroviral agent used in the treatment of AIDS) and Cyclosporine (an antifungal agent). Their successful release from exines into different media in vitro and in vivo (carried out in Beagle dogs) was shown. These in vivo experiments highlighted the need for extra protection of the drug from the GI tract and additional coatings were applied to sporopollenin exines, including a soluble form of sporopollenin. Exines with coatings were assessed to ensure they were still able to degrade in blood and release the encapsulated substance. Current results are highly indicative that sporopollenin could become a practicable oral delivery system for molecules that are otherwise problematic to administer, such as protein drugs that degrade rapidly in acidic conditions.
2
Salvage, Jonathan Peter. „A novel phosphorylcholine-based nanoparticulate drug delivery system“. Thesis, University of Brighton, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.499068.
Der volle Inhalt der QuelleAnnotation:
Phosphorylcholine (PC) based materials have been shown to have increased biocompatibility when compared to more established bio-implantable materials. This has been attributed to the ability of PC to mimic the cell lipid bilayer membrane, resulting in reduced protein adhesion and cellular interaction / activation. PC research has previously focused on the areas of contact lens formulation and medical device coating. This project sought to harness the biomimetic properties of PC to develop novel systems for drug delivery, with the emphasis being focused on microparticulate drug delivery.
3
MODICA, DE MOHAC Laura. „Novel Drug Delivery System for Treatment-Resistant Schizophrenia“. Doctoral thesis, Università degli Studi di Palermo, 2021. http://hdl.handle.net/10447/478483.
Der volle Inhalt der Quelle
4
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.
Der volle Inhalt der Quelle
5
Mawad, Damia Graduate School of Biomedical Engineering Faculty of Engineering UNSW. „Development of Novel hydrogels for protein drug delivery“. Awarded by:University of New South Wales. Graduate School of Biomedical Engineering, 2005. http://handle.unsw.edu.au/1959.4/25221.
Der volle Inhalt der QuelleAnnotation:
Introduction: Embolic agents are used to block blood flow of hypervascular tumours, ultimately resulting in target tissue necrosis. However, this therapy is limited by the formation of new blood vessels within the tumour, a process known as angiogenesis. Targeting angiogenesis led to the discovery of anti-angiogenic factors, large molecular weight proteins that can block the angiogenic process. The aim of this research is development of poly (vinyl alcohol) (PVA) aqueous solutions that cross-link in situ to form a hydrogel that functions as an embolic agent for delivery of macromolecular drugs. Methods: PVA (14 kDa, 83% hydrolysed), functionalised by 7 acrylamide groups per chain, was used to prepare 10, 15, and 20wt% non-degradable hydrogels, cured by UV or redox initiation. Structural properties were characterised and the release of FITCDextran (20kDa) was quantified. Degradable networks were then prepared by attaching to PVA (83% and 98 % hydrolysed) ester linkages with an acrylate end group. The effect on degradation profiles was assessed by varying parameters such as macromer concentration, cross-linking density, polymer backbone and curing method. To further enhance the technology, radiopaque degradable PVA was synthesised, and degradation profiles were determined. Cell growth inhibition of modified PVA and degradable products were also investigated. Results: Redox initiation resulted in non-degradable PVA networks of well-controlled structural properties. Increasing the solid content from 10 to 20wt% prolonged the release time from few hours to ~ 2 days but had no effect on the percent release, with only a maximum release of 65% achieved. Ester attachment to the PVA allowed flexibility in designing networks of variable swelling behaviors and degradation times allowing ease of tailoring for specific clinical requirements. Synthesis of radiopaque degradable PVA hydrogels was successful without affecting the polymer solubility in water or its ability to polymerize by redox. This suggested that this novel hydrogel is a potential liquid embolic with enhanced X-ray visibility. Degradable products had negligible cytotoxicity. Conclusion: Novel non-degradable and radiopaque degradable PVA hydrogels cured by redox initiation were developed in this research. The developed PVA hydrogels showed characteristics in vitro that are desirable for the in vivo application as release systems for anti-angiogenic factors.
6
Babu, Kavitha Mary Vadakkel. „The Development of a Novel Controlled Release Drug Delivery System“. The University of Waikato, 2007. http://hdl.handle.net/10289/2590.
Der volle Inhalt der QuelleAnnotation:
The aim of this research was to formulate, characterise and assess the feasibility of a novel drug delivery system known as the in situ gelling matrix (ISGM) where a hydrophilic polymer is suspended in a non-aqueous solvent that converts into a gel when injected subcutaneously or intramuscularly thus giving a controlled release matrix for a drug. Although the concept has been patented with claims that this kind of drug delivery is achievable in theory for a wide variety of candidate substances, actual formulation studies for making a commercially viable product for this technology are completely lacking in practice. The research embodied in this thesis addresses this lack. Initial studies involved conducting a biocompatibility study using the HET-CAM (hens egg test - chorioallantoic membrane) test on a range of possible ingredients for the delivery system. The materials deemed biocompatible were then carried through to a screening process where the physical stability of the hydrophilic polymers in non-aqueous solvents was monitored. It was found that the hydrophilic polymers tested sedimented rapidly in the non-aqueous solvents indicating such a system was not physically stable. Consequently, density-inducing or viscosity-inducing agents were added to the non-aqueous solvents to retard the sedimentation rate. The addition of polycarbophil, a viscosity-inducing agent, clearly increased the viscosity of the system. However, undesirable formation of polycarbophil globules occurred during the manufacturing process, which caused batch-to-batch variations in the viscosity of the continuous phase. Various manufacturing methods were tested before arriving at the optimum procedure to prevent globule formation using a high speed dispersion tool. A final physical sedimentation analysis of candidate continuous phases and hydrophilic polymers was conducted for determining the ideal combination of ingredients to use in the system. These investigations finally led to the adoption of an optimum mix of components consisting of 10% (w/w) hydroxypropyl methylcellulose (HPMC) (the hydrophilic polymer) suspended in a continuous phase of propylene glycol (the non-aqueous solvent) containing 0.67% (w/w) polycarbophil (the viscosity inducing agent). Using this mix of components, the in situ gelling matrix system was then subjected to various characterisation studies including infrared (IR), differential scanning calorimetry (DSC), ultraviolet-visible (UV-Vis) spectrophotometry and redispersion studies. The chemical stability of the hydrophilic polymer and the continuous phase (the non-aqueous solvent and polycarbophil) was monitored and were found to be chemically stable over a 9 month period. The feasibility of the in situ gelling matrix technology as a controlled release device was assessed using the drug propranolol. In vitro drug release studies were conducted using a custom-built dissolution apparatus. The effect of various parameters such as the concentration of the hydrophilic gelling agent on the drug release rate was investigated. Increasing the concentration of the gelling agent in the formulation resulted in a slower rate of release. The drug release data were modelled using the Higuchi relationship and a power law relationship to compare the effects of the various parameters on the release rate Stability studies on the drug in the in situ gelling matrix system were carried out by storing samples in accelerated ageing conditions of 40 C / 75% relative humidity for 4 weeks. During this time, the samples were analysed each week by high performance liquid chromatography (HPLC). These demonstrated that no apparent drug degradation had occurred over the 4-week period. This indicates that the drug propranolol in the in situ gelling matrix system is stable under ambient conditions for at least 4 weeks. The results of this study demonstrated that the in situ gelling matrix technology is potentially viable as a drug delivery system and provide a practical methodology for the commercial development of such systems.
7
Sy, Jay Christopher. „Novel strategies for cardiac drug delivery“. Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/39531.
Der volle Inhalt der QuelleAnnotation:
The American Heart Association (AHA) estimates that at least one American will die from a coronary event every minute, costing over $150 billion in 2008 alone. Regenerating the myocardium of patients that survive the initial infarction has proven to be an elusive goal. A variety of factors - including the loss of contractile cells, inflammatory response following infarction, cardiac hypertrophy, and lack of suitable cues for progenitor cells - causes fibrosis in the heart and loss of cardiac function. This dissertation examines three drug delivery strategies aimed at improving conditions for cardiac regeneration: polyketal microspheres as non-inflammatory drug delivery vehicles; surface functionalization of microparticles with nitrilotriacetic acid-nickel (NTA-Ni) for non-covalent tethering of proteins; and using Hoechst-inspired ligands for targeting extracellular DNA in necrotic tissue.
8
Venugopal, Balaji. „Preclinical evaluation of a novel drug delivery system for cisplatin“. Thesis, University of Glasgow, 2012. http://theses.gla.ac.uk/4198/.
Der volle Inhalt der QuelleAnnotation:
The aim of this body of work was to characterise a novel cisplatin drug delivery system and to develop new tools based on biophotonic imaging that could be used to enhance studies of drug delivery in vivo. Cucurbiturils (CB) are macrocycles which are formed by acid catalysed condensation of glycoluril and formaldehyde. The internal cavity of CB[7] encapsulates a single molecule of cisplatin and the hypothesis was that encapsulation would reduce thiol degradation of the drug. Drug sensitivity studies in vitro with the cisplatin-sensitive human ovarian cancer cell line, A2780, and a cisplatin-resistant derivative, A2780/cp70, showed that the CB[7] encapsulated cisplatin retained activity but that this encapsulation drug delivery system was not able to overcome resistance to platinum. However, when these cell lines were grown as subcutaneous xenografts in nu/nu mice, the encapsulated cisplatin was able to reduce the growth of A2780/cp70 tumours which are resistant to the maximum tolerated dose of cisplatin in vivo. One possible explanation of this observation is that encapsulation might alter the pharmacokinetics of cisplatin and a method for the detection of platinum in biological samples by ICP-MS was established and validated. This assay was sufficiently sensitive to detect the low levels of platinum present in mouse plasma 24 hours after administration of either free or encapsulated cisplatin. Plasma and tissue pharmacokinetics show that encapsulation had no effect on the peak plasma concentration of cisplatin but did reduce the rate at which cisplatin was cleared from the plasma. The increased plasma AUC of cisplatin resulted in a non-selective increase in the delivery of cisplatin to both tumour and normal tissues. However, there was no apparent increase in toxicity which could be explained by the fact that encapsulation, unlike an increase in the dose of free cisplatin, had no effect on the peak plasma concentration. Subcutaneous xenografts lack critical features of human tumours. The development of more complex models for use in drug development has been limited due to lack of a method for monitoring tumour growth. Biophotonic imaging was, therefore, investigated to determine whether it is sufficiently sensitive and reproducible to be able to evaluate growth of disseminated tumours in mice. The bioluminescent signal is dependent on the metabolism of luciferin by luciferase. Subcutaneous injection of luciferin was shown to produce a consistent signal in all injected mice. The bioluminescent signal was transient but reached a maximum intensity 6 minutes after injection and remained stable for about 4 minutes which defined the window during which measurements were taken. Sensitivity was shown to be dependent on the level of expression of luciferase by the cells. Injection of commercially available HCT116Luc cells, where the luciferase gene was inserted by a lentiviral system, was shown to allow detection of 10,000 cells in the lungs of mice. This sensitivity was about 10 fold greater than was obtained by lipofectamine based gene transfection. When HCT116Luc cells were grown as subcutaneous xenografts in mice, an exponential growth pattern was easily detected by bioluminescence imaging and the reproducibility between mice was comparable to that routinely obtained by calliper measurements. Activity of encapsulated cisplatin was determined in a model of disseminated ovarian cancer. Rab25, a member of the RAS oncoprotein superfamily, is up-regulated in around 80% of ovarian cancer samples compared to normal ovarian epithelium. Rab25 contributes to tumour progression by enabling the tumour cells to invade the extracellular matrix by altering the trafficking of integrin. Transfection of Rab25 into A2780 cells results in cells that can grow in the peritoneal cavity of mice. A2780-Rab25 cells were 4 fold resistant to cisplatin in vitro which confirms a previous observation that Rab25 expression in A2780 makes them less sensitive to the induction of apoptosis in response to stress. A2780-Rab25 cells that express the luciferase gene (A2780-Rab25Luc) were injected into the peritoneal cavity of mice and growth was measured by biophotonic imaging. Exponential growth was clearly apparent at a stage at which no obvious abdominal distension was apparent. The disseminated A2780-Rab25Luc tumour xenografts were less sensitive to cisplatin than are subcutaneous xenografts of A2780. This is the first study that suggests that Rab25 over-expression results in reduced drug sensitivity in vivo. In contrast, a very significant growth inhibition was observed when mice were treated with an equivalent dose of encapsulated cisplatin regardless of whether it was administered by the intraperitoneal or subcutaneous route. These results are very encouraging since they confirm the enhanced activity of encapsulated cisplatin and also demonstrate the value of biophotonic imaging for measurement of tumour growth in vivo. Pharmacodynamic measures of drug activity in vivo in animal models are often based either on measures of surrogate tissue response or on single measures on tumour tissue removed at the end of the experiment. Biophotonic imaging in vivo allows the translation of reporter assays used in cell lines in vitro to studies of tumour response in vivo. A plasmid was prepared that links the p53 transcriptional response element to the luciferase gene and it was then transfected in to A2780 cells which express wild type p53. Stable transfectants of A2780p53Luc were treated with cisplatin, doxorubicin and paclitaxel and induction of p53 determined by bioluminescence and confirmed by Western blotting. A very low bioluminescent signal was present in untreated cells and a clear dose dependent increase in bioluminescence was seen in response to all three drugs. When A2780p53Luc cells were grown as subcutaneous xenografts the bioluminescent signal was significant in untreated tumours but was markedly increased 24 hours after treatment of the mice with cisplatin. Induction of p53 in the tumours was confirmed by immunohistochemistry and this also confirmed significant expression of p53 in untreated tumours. The possible implications of these findings for the improved delivery of cisplatin are discussed.
9
Svirskis, Darren. „Development of a novel drug delivery system based on conducting polymers“. Thesis, University of Auckland, 2010. http://hdl.handle.net/2292/6568.
Der volle Inhalt der QuelleAnnotation:
Controlled release systems offer advantages over conventional therapies by maintaining drug concentrations at therapeutically desired levels whilst simultaneously improving compliance. Intrinsically Conducting Polymers (ICP) are organic materials that have electrical, magnetic and optical properties usually associated with metals, whilst retaining the advantageous mechanical properties and ease of processing usually associated with polymers. A novel drug delivery system, based on the ICP polypyrrole (PPy), has been developed to provide for the controlled release of risperidone. Due to the inherent properties of ICPs, electrical stimulation can be used to alter the redox state of PPy, which in turn can modify the release rate of drug. A validated, specific, stability indicating high performance liquid chromatography (HPLC) analytical method was used to quantify drug release from PPy films. PPy was selected as the platform material for drug delivery due to its inherent conductivity, ease of preparation and apparent biocompatibility. Various anionic dopants were trialled in the preparation of PPy films - p-toluene sulfonate produced the optimal formulation (PPy-pTS). PPy-pTS films were prepared containing risperidone (8.2 % w/w). Drug release profiles could be altered by applying different electrical stimulation. The rate of drug release could be increased or decreased by applying or withholding electrical stimulation. Atomic Force Microscopy was used to investigate changes in PPy film thickness when different stimuli were applied. The highest levels of drug release were observed when PPy was reduced; this was accompanied by expansion of the film. In order to be used clinically, the films must be functional over a defined shelf life. Stability studies suggested polymer morphology altered over time, accompanied by changes in risperidone release. In general, while aging slowed the rate of risperidone release from PPy films, release rates could be altered through electrical signalling in polymer films stored for up to 4 weeks at 40 ��C. This project relied on the multidisciplinary collaboration of pharmaceutical scientists, chemists and clinicians. The described technology could be utilised for implantable drug delivery devices, where the dose could be adjusted by external signalling, optimising patient benefit to side effect ratios while simultaneously ensuring compliance.
10
Gaspar, Diana Patrícia Rodrigues. „Novel strategy to produce a drug delivery system for skin regeneration“. Master's thesis, Universidade da Beira Interior, 2012. http://hdl.handle.net/10400.6/1118.
Der volle Inhalt der QuelleAnnotation:
Skin lesions are traumatic events that lead to the increase of fluid loss, infections, scarring and locally immunocompromised regions. These injuries can be caused by genetic disorders, acute trauma or even surgical interventions. In these situations, a substantial area of skin can be damaged, often without the possibility of being regenerated. Scientists have put a lot of effort in the development of suitable drug delivery systems suitable to release therapeutic molecules that are required for the initials phases of the wound healing process. Cell microencapsulation arises as an alternative approach for sustained in situ cell delivery. This technology is based on the immobilization of cells within a polymeric matrix, surrounded by a semi-permeable membrane, that isolate the encapsulated cells from the host immune system. Nonstanding, the microparticulate matrix still allows the exchange of nutrients, gases, waste and releasing of bioactive molecules, such as extracellular matrix components and growth factors secreted by cells. Nevertheless, the optimization of cell-based therapy demands the development of alternative strategies to improve cell administration. Alginate has been used for cell microencapsulation, due to its simple gelling process, excellent biocompatibility, biodegradability properties and its stability under in vivo conditions. On the other hand, nanoparticulate systems have been widely used in the biomedical field, as drug delivery devices that can improve the efficiency and widening the applications of the microencapsulation systems. Therefore, the present study aimed to develop biodegradable alginate microparticles that were used for human fibroblasts cells and chitosan nanoparticles encapsulation, in order to improve the wound healing process. To do so, two types of microparticles were firstly produced with alginate and a mixture of alginate and collagen. Subsequently, these carriers were characterized according to their size and geometry by scanning electron microscopy. Confocal images were also acquired to confirm cell encapsulation in microparticles. The cytotoxic profile of the carriers was assessed. Cell release from microparticles was observed over time after encapsulation through optical microscopic analysis. In second part of the work, chitosan nanoparticles loaded with a model protein (bovine serum albumin) were produced and were incorporated in microparticles. The encapsulation efficiency of this protein in nanoparticles was determined. Then, both the morphology and size of these nanoparticles were characterized. The results herein obtained showed that the developed microparticles and nanoparticles can be used as systems tailored for sustainable cells and drug release.As lesões na pele são acontecimentos traumáticos que levam ao aumento da perda de fluidos, a infecções, à formação de cicatrizes e ao aparecimento de regiões imunocomprometidas. Estas feridas podem ser causadas por desordens de origem genética, traumas ou mesmo devido a cirurgias. Deste modo, uma área substancial da pele pode ser danificada, muitas vezes sem a possibilidade de regeneração. Os investigadores têm procurado desenvolver novos sistemas de entrega de drogas, de forma a acelerar o processo de cicatrização. O microencapsulamento celular surgiu recentemente como uma nova abordagem, para entrega controlada e de longa duração de agentes terapêuticos produzidos e secretados pelas próprias células, tais como componentes da matriz extracelular e factores de crescimento, os quais são essenciais para a regeneração. Esta tecnologia tem por base a imobilização de células, dentro de uma matriz polimérica rodeada por uma membrana semi-permeável. Assim, as células não são reconhecidas pelo sistema imunitário do hospedeiro e a membrana permite a difusão de nutrientes e gases para o interior da matriz e a saída das moléculas bioactivas secretadas pelas células e dos resíduos resultantes do metabolismo celular. No entanto, a terapia celular necessita ainda de ser optimizada. O alginato é um polímero que tem sido usado para o encapsulamento celular, devido ao seu fácil processo de gelificação, excelente biocompatibilidade, biodegradabilidade e estabilidade in vivo. Por outro lado, os sistemas nanoparticulados têm sido amplamente utilizados em aplicações biomédicas, por exemplo na produção de dispositivos de entrega direcionada de moléculas bioactivas, uma vez que permitem obter um perfil de libertação controlado. O presente trabalho teve como objectivo o desenvolvimento de micropartículas de alginato para encapsular fibroblastos humanos e nanopartículas de quitosano, com o intuito de futuramente serem usadas como agentes promotores da cicatrização de feridas. Inicialmente, foram produzidos dois tipos de micropartículas, um à base de alginato e outro de alginato com colagénio. As micropartículas produzidas foram caracterizadas quanto ao seu tamanho e geometria por microscopia electrónica de varrimento. Posteriormente, foram também adquiridas imagens de confocal para confirmar o encapsulamento de células nas micropartículas. O perfil citotóxico dos transportadores foi caracterizado através de testes de viabilidade celular, os quais confirmaram a biocompatibilidade dos transportadores. O perfil de libertação das células foi observado por análise microscópica ao longo dos dias. Numa segunda parte do trabalho foram produzidas nanopartículas de quitosano com o objetivo de serem incorporadas nas micropartículas como transportadores de factores de crescimento e, assim, favorecer a cicatrização das feridas. A eficiência de encapsulação das nanopartículas foi avaliada através da incorporação de uma proteína modelo, albumina de soro bovino. Posteriormente fez-se a caracterização da morfologia e do tamanho destas nanopartículas. Os estudos efectuados demonstraram que o sistema desenvolvido é adequado para a libertação de células e moléculas bioativas de forma controlada, prolongada e em concentrações fisiológicas.
11
Lungare, Shital. „Development of novel delivery systems for nose-to-brain drug delivery“. Thesis, Aston University, 2017. http://publications.aston.ac.uk/37491/.
Der volle Inhalt der QuelleAnnotation:
The blood brain barrier (BBB) poses a significant hurdle to brain drug delivery. However, the location of the olfactory mucosa, within the nasal cavity, is a viable target site for direct nose-to-brain (N2B) delivery, thereby bypassing the BBB. To exploit this target site innovative nasal formulations are required for targeting and increasing residency within the olfactory mucosa. We developed and characterised three formulation systems for N2B delivery, (i) thermoresponsive mucoadhesion nasal gels sprays; (ii) mesoporous silica nanoparticles and (iii) nasal pMDI devices. We developed an optimal mucoadhesive formulation system incorporating amantadine as a model, water-soluble anti-Parkinson’s drug using carboxymethy cellulose and chitosan as mucoadhesives. Formulations demonstrated droplet sizes of < 130mm and stability over 8-weeks when stored at refrigeration conditions with no significant cellular toxicity against olfactory bulb (OBGF400) and nasal epithelial (RPMI 2650) cells. Mesoporous silica nanoparticles (MSNP) were prepared (~220nm) and demonstrated cellular uptake into OBGF400 within 2-hours of incubation with minimal toxicity. MSNP were loaded with two novel phytochemicals known to possess CNS activity, curcumin and chrysin, with loading efficiencies of ~12% confirmed through TGA, DSC and HPLC-UV analysis. Furthermore, a pH dependant release profile was identified with curcumin with greater release at nasal cavity pH 5.5 compared to pH 7.4. Furthermore, successful incorporation of MSNP into nasal gels was demonstrated through rheological studies with a decrease in Tsol-gel. A pilot study was conducted to assess the feasibility of modified existing pulmonary pMDI to deliver diazepam intranasally, targeting the olfactory mucosa. Diazepam was formulated with HFA134a and using ethanol as a co-solvent, and demonstrated stability in formulation over 3 months. Deposition studies within a nasal cast model demonstrated 5-6% deposition onto the olfactory mucosa under optimal administration conditions in the absence of any nozzle attachments. Our studies have provided a basis for the development to innovative intranasal formulation systems potentially capable of targeting the olfactory mucosa for both water soluble and poorly soluble drugs.
12
Bostanian, Levon Artine. „Novel drug delivery systems for relatively insoluble substances /“. The Ohio State University, 1995. http://rave.ohiolink.edu/etdc/view?acc_num=osu14878617968179.
Der volle Inhalt der Quelle
13
Lucato, Arianna <1991>. „Computational design of novel protein-drug delivery systems“. Master's Degree Thesis, Università Ca' Foscari Venezia, 2019. http://hdl.handle.net/10579/16136.
Der volle Inhalt der QuelleAnnotation:
Cancer is one of the leading causes of death throughout the world and the number of cases per year is reported to rise to 23.6 million by 2030. Amongst the different types of treatments available, chemotherapy represent the most common one. Despite its proven capability of tumour shrinkage and prevention from coming back after surgery, several factors limit its potential. These include poor bioavailability and biodistribution of the majority of the chemotherapeutic agents commonly used, the high dose required, their numerous adverse side effects, the development of drug resistance and non-specific targeting.
To overcome these limitations, I propose to develop novel protein-based drug delivery system capable of selectively transporting large quantities of chemotherapeutics at the tumour-site thus conferring greater therapeutic indices and efficacy. The new systems are based on proteins, natural existing polymers, that have the intrinsic property of binding small molecules with high affinity and specificity.
The project is structured in two phases. In the first phase I applied FuncLib, an automated method that uses phylogenetic analysis and Rosetta design calculations, to design mutants with higher affinity toward two selected chemotherapeutic agents. In the second phase, fifty-five designs were selected according to G Rosetta energy score and structural diversity, synthesised and assembled using a repertoire of molecular biology techniques.
14
Espeleta, Gonzalez David <1995>. „DEVELOPMENT OF NOVEL PROTEIN-BASED DRUG DELIVERY SYSTEMS“. Master's Degree Thesis, Università Ca' Foscari Venezia, 2021. http://hdl.handle.net/10579/19858.
Der volle Inhalt der QuelleAnnotation:
Cancer is a vast group of diseases caused by mutations in the human DNA that result in an uncontrollable growth of cells which can spread around the body. Cancer is one of the leading causes of mortality worldwide.
Advancements in CTXs allowed the development of effective treatments. However, most CTX agents present poor pharmacokinetic and safety profiles. Development of appropriate drug carriers is one of the potential solutions for counteracting these drawbacks.
The aim of this thesis is to make advancements in the engineering of a protein based carrier, with higher binding affinity to the CTX agents. Furthermore, explore the expression of fusion proteins with the aim of improving the characteristics of the delivery system.
In the first phase of the project, 55 genes, corresponding to human serum albumin (HSA) mutants previously engineered to have higher binding affinity to doxorubicin or 9-aminocamptothecin, were cloned by Gibson assembly (GA). 52 of these mutants were then successfully expressed in a yeast display system, which will be used for future binding affinity experiments.
For the second part of this thesis, a cloning system using restriction enzymes (RE) was designed in order to produce a series of HSA oligomers. The HSA dimer was successfully cloned, expressed, and purified. However it showed a complete degradation over time. Therefore, alternative cloning strategies or changes in the design of the linker between the monomers should be employed.
15
Lee, Wang Wang. „Factors affecting drug release and absorption from a novel oral delayed release drug delivery system“. Thesis, Durham University, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269886.
Der volle Inhalt der Quelle
16
Gerrard, Stephen Edmund. „A novel infant therapeutic delivery system for drugs, nutrients and anti-viral agents“. Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648462.
Der volle Inhalt der Quelle
17
Challis, Deborah. „Physicochemical and biopharmaceutical studies of novel self-emulsifying systems for administration by the oral route (SEDDS)“. Thesis, University of Bath, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.280871.
Der volle Inhalt der Quelle
18
O'Hear, Carol E. „Antibody buffering : a novel mechanism of drug delivery /“. Thesis, Connect to this title online; UW restricted, 2004. http://hdl.handle.net/1773/5024.
Der volle Inhalt der Quelle
19
Zhang, Feng. „Hot-melt extrusion as a novel technology to prepare sustained-release dosage forms /“. Digital version accessible at:, 1999. http://wwwlib.umi.com/cr/utexas/main.
Der volle Inhalt der Quelle
20
Turner, Jonathan D. „Development of a novel in vitro system for nasal drug delivery development“. Thesis, Aston University, 2000. http://publications.aston.ac.uk/10987/.
Der volle Inhalt der QuelleAnnotation:
The work in this thesis represents the development of an in vitro model system in which the interior characteristics of the nasal cavity are closely represented, and solid or minimal volume dosage forms can be investigated. The complete nasal chamber consists of two sections: a lower tissue, viability chamber and an upper nasal chamber. The lower tissue viability chamber has been shown, using existing tissue viability monitoring techniques, to maintain the viability of a number of epithelial tissues, including porcine and rabbit nasal tissue, and rat ileal and Payers' patch tissue. The complete chamber including the upper nasal chamber has been shown to provide tissue viability for porcine and rabbit nasal tissue above that available using the existing Ussing chamber techniques. Adaptation of the complete system, and the development of the necessary experimental protocols that allow aerosol particle-sizing, together with videography, has shown that the new factors investigated, humidity and airflow, have a measurable effect on the delivered dose from a typical nasal pump. The system developed in this thesis has been shown to be flexible, in allowing the development of the confocal and particle-sizing systems. For future nasal drug delivery studies, the ability to measure such factors as the size of the delivered system in the nasal cavity, the depth of penetration of the formulation into the tissue are essential. Additionally, to have access to other data such as that obtained from drug transport in the same system, and to have the tissue available for histological examination represents a significant advance in the usefulness of such an in vitro technique for nasal delivery.
21
Donnelly, L. „Synthesis and characterisation of novel polymeric drug delivery systems“. Thesis, Queen's University Belfast, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.398150.
Der volle Inhalt der Quelle
22
Liu, Yang. „Development of Novel Drug Delivery Systems for Cancer Therapy“. The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu153105342400785.
Der volle Inhalt der Quelle
23
Phan, Tu-Ai Thi. „Novel host-guest systems for ultrasound-mediated drug delivery /“. Available to subscribers only, 2007. http://proquest.umi.com/pqdweb?did=1459908051&sid=2&Fmt=2&clientId=1509&RQT=309&VName=PQD.
Der volle Inhalt der Quelle
24
Basu, Sarkar Arindam Kochak Gregory Michael. „Carbohydrate nanoparticles a novel drug delivery platform for the systemic route /“. Auburn, Ala., 2006. http://repo.lib.auburn.edu/2006%20Summer/Dissertations/BASU_SARKAR_26.pdf.
Der volle Inhalt der Quelle
25
Misirlis, Dimitrios. „Development of a novel drug delivery system based on polymeric, thermoresponsive, hydrogel nanoparticles /“. [S.l.] : [s.n.], 2005. http://library.epfl.ch/theses/?nr=3362.
Der volle Inhalt der Quelle
26
Fisher, Karen Ann. „Development of a novel drug delivery system using macrophages and inorganic porous materials“. Thesis, De Montfort University, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.434031.
Der volle Inhalt der Quelle
27
Carradori, Dario. „Novel nanoparticle-based drug delivery system for neural stem cell targeting and differentiation“. Thesis, Angers, 2017. http://www.theses.fr/2017ANGE0056/document.
Der volle Inhalt der QuelleAnnotation:
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
28
Gevorgyan, S. „NOVEL POLY(AMIDOAMINE) NANOPARTICLES DESIGNED FOR DRUG DELIVERY TO THE CENTRAL NERVOUS SYSTEM“. Doctoral thesis, Università degli Studi di Milano, 2016. http://hdl.handle.net/2434/366799.
Der volle Inhalt der QuelleAnnotation:
With the aging population, central nervous system diseases are becoming increasingly widespread. However, the treatment of such diseases represents a challenge mainly due to the presence of the blood-brain barrier, which effectively blocks most of drugs to pass into the central nervous system and impedes the treatment of diseases. Therefore, effective ways of drug transport to the central nervous system are highly required.
Polymeric nanoparticles are drug delivery vectors that have high specificity to their targeted sites and increasingly enhance the stability of encapsulated drugs. Poly(amidoamines) are a promising family of synthetic polymers that can be used in nanoparticles synthesis. Nanoparticles synthesized from linear poly(amidoamines) show very good biocompatibility levels and specific targeting properties. Nevertheless, those nanoparticles are mainly synthesized by self-assembly and usually lack long-term stability.
In this study we developed innovative poly(amidoamine) nanoparticles synthesized by ultraviolet light assisted photo-crosslinking. The synthesis method had an advantage of being simple, did not require toxic organic solvents and was shown to be easily scaled-up. Moreover, poly(amidoamine) nanoparticles were coated by Polysorbate 80 surfactant, which not only increased the nanoparticles stability but also gave them central nervous system targeting properties. Poly(amidoamine) nanoparticles were able to successfully encapsulate model therapeutic compounds and release them in a slow and controlled manner. Furthermore, the nanoparticles showed high permeability levels across an in vitro blood brain barrier model.
The developed poly(amidoamine) nanoparticles show great potential to be used as delivery vectors to the central nervous system.
29
Rizi, Khalida. „Novel Bio-Responsive Drug Delivery Systems to Treat Atopic Dermatitis“. Thesis, University of Reading, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.533776.
Der volle Inhalt der Quelle
30
Kolhe, U. D. „Synthesis and evaluation of polymers for novel drug delivery systems“. Thesis(Ph.D.), CSIR-National Chemical Laboratory, Pune, 2011. http://dspace.ncl.res.in:8080/xmlui/handle/20.500.12252/3825.
Der volle Inhalt der Quelle
31
Mukhopadhyay, Debashis, und n/a. „Preparation and evaluation of novel drug alginate granule systems using paracetamol as model drug“. University of Otago. School of Pharmacy, 2006. http://adt.otago.ac.nz./public/adt-NZDU20070503.143431.
Der volle Inhalt der QuelleAnnotation:
Purpose: The aim of this thesis was to investigate a novel method of preparing crosslinked alginate matrices. Current methods use large quantities of water and hence are not suitable for large scale manufacturing of drug alginate particulate systems. Moreover, the current processes offer little scope for control of the crosslinking process. The aim was to overcome these problems through studies of paracetamol alginate granular matrices prepared by the novel method and to explore if these granules could be used to improve the taste of paracetamol.
Methods: The novel method involves preparation of dried drug alginate granules (moisture content: <5-6 %) using conventional granulation followed by crosslinking treatment of the dried granules with calcium chloride or a combination of calcium and magnesium ion solution in a crosslinking bath. The effect of the process (shear rate, binder quantity) to prepare untreated granules, composition of the raw materials (drug particle size and type of alginate) and subsequently the crosslinking treatment process variables (Ca�⁺ ion concentration, agitation rate, time and temperature of Ca�⁺ solution) on the physicochemical properties of granule systems were studied using factorial designs together with supporting studies.
The granules were characterized using sodium and calcium content analysis, drug release studies (mainly sub-60s release) matrix swelling rate and equilibrium swelling studies, tensile strength studies, ion permeation studies, SEM and X Ray analysis and gravimetric studies. Sensory studies correlating sub-60 s drug release (determined using a specially designed apparatus) and human taste scores (measured using an analogue scale) were then undertaken. Selected formulations were evaluated for taste improvement and to determine if mucoadhesion led to an increased unpalatability of paracetamol.
Results: Of the crosslinking treatment factors, the calcium concentration had the greatest effect on crosslinked granules. Although other treatment factors also affected the granule properties, alteration of the salt concentration allowed considerable control over the crosslinking process (not possible in the conventional method) in addition to providing a mechanistic understanding of the crosslinking process in the dried state. The use of low calcium concentrations (< 20 mg/ml, CaCl₂. 2H₂O) during treatment led to granule erosion (hence drug loss) due to overall incomplete crosslinking but led to a reduction in the short-term drug release compared to the granules treated with intermediate (100- 250 mg/ml) or high calcium concentrations (>400 mg/ml) due to reduction in the granule porosity after crosslinking. Although intermediate calcium concentrations led to complete crosslinking and longer release times (T 85 %: 25 min) high calcium crosslinking restricted the crosslinking to the surface of the granules leading to faster drug release (T 85 %: 8 min) with low calcium granules showing intermediate crosslinking and drug release rates (T 85 %: 18 min). High calcium treatment limited drug loss during crosslinking (95 % recovered compared to 83 % recovery at intermediate calcium concentration) without affecting the short-term drug release much. Low calcium granules showed the lowest drug recovery (< 70 %) and slowest sub-60s drug release followed closely by intermediate and high calcium treated granules.
The granule preparation factors (shear rate, binder quantity) and type of alginate used, considerably affected the sub-60s drug release by affecting surface porosity especially when a low shear rate was used. However, these factors only slightly reduced the drug loss during crosslinking treatment phase (about 4 % increase in drug recovery). Smaller drug particle size had a slightly larger incremental effect on drug recovery (about 8 % increase in the drug recovery) during crosslinking treatment due to better embedding of the drug particles inside the untreated granule matrix. This was true as long as the particle size of the drug was > 98 [mu]m. Below this size drug recovery remained unaffected by changes in drug particle size. Although granule surface porosity considerably affected the sub-60s drug release, its effect on drug release (long-term) was much less.
A linear correlation was observed between the sub-60s drug release and sensory scores despite high individual variability. Both granule formulations evaluated showed taste improvement and mucoadhesion did not lead to an increase in the bitter taste of the uncrosslinked paracetamol alginate granules.
Conclusions: Unlike the traditional method, the new technique of preparation of crosslinked drug alginate particulate systems uses very little water and allows greater control over the the crosslinking process compared to the swollen state crosslinking. The novel process of preparation is versatile, and should be scalable. It offers the formulator a platform to prepare a matrix, reservoir or a combination of these two systems using alginates and other drugs and polymers as well. Adequate short-term control over paracetamol release, very little loss of paracetamol during treatment (< 5 % loss), reduction in mucoadhesion of the granules and lastly improvement of the taste of paracetamol is possible using alginate based systems especially if high calcium is used during the crosslinking treatment. Hence, it is likely that these taste-improved granules could be used to prepare tablets without the need for a protective film coating to improve taste. Finally, this research established the utility of short-term drug release in taste improvement research and characterization of solid controlled release dosage forms.
32
Pavuluri, Nina. „Development and evaluation of drug-admicelle systems for poorly soluble drugs : a novel surfactant templated drug delivery platform /“. Full text available from ProQuest UM Digital Dissertations, 2008. http://0-proquest.umi.com.umiss.lib.olemiss.edu/pqdweb?index=0&did=1781035201&SrchMode=1&sid=1&Fmt=2&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1258661510&clientId=22256.
Der volle Inhalt der QuelleAnnotation:
Thesis (Ph.D.)--University of Mississippi, 2008.Typescript. Vita. Major advisor: John O' Haver "June 2008." Includes bibliographical references (leaves 120-163). Also available online via ProQuest to authorized users.
33
Fransén, Nelly. „Studies on a novel powder formulation for nasal drug delivery /“. Uppsala : Acta Universitatis Upsaliensis Acta Universitatis Upsaliensis, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-9292.
Der volle Inhalt der Quelle
34
Cheung, Wai-Han. „Novel steroidal metal complexes with potential pharmaceutical applications“. Thesis, Loughborough University, 1992. https://dspace.lboro.ac.uk/2134/27879.
Der volle Inhalt der QuelleAnnotation:
A study to develop novel lipophilic metal ion complexes based on dihydrocholesterol was undertaken. Steroid ligands functionalised at the 2- and 3- positions were synthesized as possible bidentate ligands for complexation of metal ions. Condensation of 5α-cholestan-3-one with ethyl formate in the presence of base gave 2-hydroxymethylene-5α-cholestan-3-one, and 2- acetyl-5α-cholestan-3-one was obtained by the reaction between 3- trimethylsilyloxy-5α-cholest-2-ene and acetyl chloride. Attempts to synthesize 2,3-dioximino-5α-cholestane from 5α-cholestan-3-one and 2α-hydroxy-5α-cholestan-3-one were unsuccessful. Likewise 2- methylene-5α-cholestan-3-one, which was expected to lead to other bidentate ligands, could not be prepared satisfactorily from 5α-cholestan- 3-one or 3-trimethylsilyloxy-5α-cholest-2-ene.
35
Colby, Aaron Henry. „Novel drug delivery systems: pH-responsive expansile nanoparticles & drug concentrating devices as tools for treating cancer“. Thesis, Boston University, 2008. https://hdl.handle.net/2144/30651.
Der volle Inhalt der QuelleAnnotation:
Thesis (Ph.D.)--Boston UniversityNew strategies for treatment and methods of drug delivery are required for patients suffering from cancer-the second leading cause of death worldwide. Current chemotherapeutic treatments frequently suffer from poor water solubility, systemic toxicity, poor accumulation within the target tissues and an inability to eradicate all remaining tumor following resection procedures. Nanoparticles (NPs) are extensively investigated as a means to increase drug solubility, alter biodistribution, target specific sites within the body, and minimize drug side effects and, as such, numerous NP formulations are being investigated as drug delivery devices to assist in the treatment and management of cancer. We have developed a pH-responsive expansile nanoparticle (eNP) that can encapsulate the hydrophobic chemotherapeutic agent Paclitaxel (Pax) (a poorly water soluble, yet potent chemotherapeutic agent), and deliver it specifically to the intracellular compartment of tumor cells. Paclitaxel-loaded-eNPs (Pax-eNPs) localize specifically to regions of intraperitoneal (IP) tumors and, once taken up by tumor cells, undergo a conformational change upon exposure to the mildly acidic cellular endosome that results in eNP swelling and intratumoral drug release. In this work, we describe: 1) the clinical problem and cost (both humanitarian and fmancial) of local cancer recurrence following tumor resection; 2) the eNP delivery system and, specifically, we characterize the swelling of eNPs using microscopy and tunable resistive pulse sensing techniques; 3) the in vitro activity of Pax-eNPs in breast cancer cells; 4) the improved efficacy of Pax- eNPs compared to the standard clinical formulation of Pax (i.e., Pax dissolved in Cremophor/Ethanol) in a murine model of established peritoneal mesothelioma; and, 5) the ability of eNPs to act as intratumoral, intracellular drug concentrating devices. Further investigation of this NP-based drug delivery system will facilitate a greater understanding of the materials and devices used in the delivery of chemotherapeutic agents and may lead to the clinical translation and application of eNPs.
2019-05-01
36
Wang, Han. „Developing Novel Drug Delivery Systems For Platinum-based Anticancer Drugs Using Coordination-driven Self-assembly“. Kent State University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=kent1595260147978142.
Der volle Inhalt der Quelle
37
Rattanakiat, Sakulrat. „Development of novel DNA-based nanosized drug delivery system using DNA containing unmethylated CpG dinucleotides“. 京都大学 (Kyoto University), 2009. http://hdl.handle.net/2433/126606.
Der volle Inhalt der Quelle
38
McBride, Eileen. „The development of a novel drug delivery system for the treatment of inflammatory bowel disease“. Thesis, University of Strathclyde, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.501659.
Der volle Inhalt der QuelleAnnotation:
The project concerns the development of a drug delivery system for the treatment of inflammatory bowel disease. This condition, which affects more than 2 million people in Europe alone, is characterised by inflammatory lesions which may be confined to the large bowel (ulcerative colitis) or extend through the intestinal tract (Crohn's disease). The components of disease activation lend themselves to treatment with immunomodulators such as the folate analogue methotrexate; although systemic sideeffects are significant. :. To o overcome this limitation, a local delivery system was investigated. In this thesis, folate has been used as a safer surrogate in the development of a silicone ribbon-based oral dosage form.
39
Liu, Quan. „Development of a novel gastro-retentive delivery system using alfuzosin HCl as a model drug“. Diss., Temple University Libraries, 2010. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/80170.
Der volle Inhalt der QuelleAnnotation:
Pharmaceutics;Ph.D.
The objectives of this project encompass the design and development of a drug delivery system to continuously deliver therapeutic agents from the stomach to the proximal region of the intestine. The delivery system designed would have sufficient gastric residence time together with near zero-order release kinetics. The physicochemical properties pertaining to the formulation development of the model drug (alfuzosin HCl) were evaluated. Excipients were selected based on the studies of their physicochemical properties and compatibility with the active ingredient. Gastro-retentive dosage forms have been the topic of interest in recent years as a practical approach in drug deliveries to the upper GI tract or for release prolongation and absorption. These dosage forms are particularly suitable for drugs that have local effects on the gastric mucosa in the stomach. Other candidates include drugs that are likely to be absorbed in the upper small intestine, or drugs that are unstable in basic environment of distal intestine and colon or those with low solubility at elevated pH conditions (i.e. weak bases). To develop a gastro-retentive delivery system the following steps were taken. First, to investigate the possible incompatibility issues between the model drug and excipients to be used for the delivery system. Stability and physicochemical properties of the active agent and its mixture with excipients were studied using analytical techniques such as Raman spectroscopy and Differential scanning calorimetry (DSC). No incompatibility issues were detected. Second, Kollidon SR as a relatively new release-rate controlling polymer was incorporated in the final formulation. For solid dosage form the ability of the final powder mix to flow well during manufacturing and the intrinsic characteristics that make it compressible are critical. The in-depth compaction study of Kollidon SR was assessed with the help of a compaction simulator. The flowability, swelling and erosion behavior together with release-rate retarding properties of Kollidon SR were also assessed. The final oral delivery system was based on Kollidon SR and Polyethylene Oxide (PEO) 303 as a monolithic matrix system. The noneffervescent monolithic matrix was made by direct compression. In vitro evaluation of the designed system released the active content in a near zero manner. The dosage form was bouyant in pH 2.0 acidic buffer with no floatation lag time which minimizes the possibility of early gastric emptying.
40
More, N. A. „Design synthesis and biological evaluation of novel heterocycles and their encapsulation in drug delivery system“. Thesis(Ph.D.), CSIR-National Chemical Laboratory, 2020. http://dspace.ncl.res.in:8080/xmlui/handle/20.500.12252/5902.
Der volle Inhalt der Quelle
41
Helfrich, Marcus Robert. „Preliminary investigations into the development of novel layered phosphonic acid vesicles for targeted drug delivery applications /“. view abstract or download file of text, 2002. http://wwwlib.umi.com/cr/uoregon/fullcit?p3045088.
Der volle Inhalt der QuelleAnnotation:
Thesis (Ph. D.)--University of Oregon, 2002.Typescript. Includes vita and abstract. Includes bibliographical references (leaves 184-193). Also available for download via the World Wide Web; free to University of Oregon users. Address: http://wwwlib.umi.com/cr/uoregon/fullcit?p3045088.
42
Farr, Dylan C. „Design and Synthesis of Novel Glycolipid Therapeutics and Drug Delivery Systems Targeting Mycobacterium tuberculosis“. Thesis, Griffith University, 2021. http://hdl.handle.net/10072/406985.
Der volle Inhalt der QuelleAnnotation:
The development of novel medicinal agents is becoming increasingly important in solving several serious healthcare issues. Tuberculosis (TB) is among one of the world’s most serious health threats, especially in developing countries, and although treatment is available, current methods take 6 – 24 months. Prolonged treatment times often result in noncompliance and subsequently result in selection for drug resistance. As there are several multidrug resistant strains of Mycobacterium tuberculosis current treatment methods are proving inadequate, and it is becoming more and more essential to develop novel drugs to control the incidence and spread of TB; alongside other pathogenic bacterial species of clinical importance. Three major approaches towards the creation of novel antitubercular and antimicrobial agents and treatment regimens through the use of carbohydrate-based chemistry were explored within this project; (i) structure-based drug design and synthesis of novel competitive inhibitors targeting mycolic acid synthesis of M. tuberculosis (Chapter 1 & 2); (ii) modification of aminoglycosides (AGs) through amphiphilic substitution, aimed to restore activity towards resistant bacteria or create agents with novel mechanisms of action (Chapter 3 & 4); (iii) the development of novel liposomal drug carriers to selectively deliver therapeutics towards severe intracellular respiratory infections (Chapter 5 & 6).
Mycolic acids are essential for the growth and survival of M. tuberculosis, making mycolic acid inhibition a highly promising drug target for treating TB. Recently, a novel pathway of fatty acid synthesis has been identified as a promising drug target. FadD32, a fatty acyl-AMP ligase (FAAL) involved in the progression of TB represents a promising target for novel drug design. A family of sulfonylacetamide compounds have shown promising preliminary results in treating TB, however these failed within in vivo experiments due to their poor pharmacokinetic properties. Further development of these lead compounds with a rational structure-based drug design approach, led to the design and synthesis of compounds directly targeting the FadD32 biosynthetic pathway. This synthesised library of compounds were evaluated for their antitubercular inhibitory effect and several lead structures were identified. The most potent derivatives synthesised within this study displayed an MIC90 of 13 – 16 μg/mL towards M. tuberculosis (H37Rv) within a normoxic resazurin reduction microplate assay.
Structural modification of the AG scaffold has historically remained a successful approach towards creating novel antibiotics. This approach led to the discovery of amikacin, a potent AG that is used for the treatment of TB today. Recently, a new class of antibiotics derived from the AG scaffold has produced several promising lead compounds that have revived antimicrobial activities against drug resistant bacterial species of clinical importance. This new class of antimicrobial agents are derived from conjugation of hydrophobic groups to AGs, creating semi-synthetic amphiphilic aminoglycosides (AAGs). AAGs have shown promising preliminary results against several drug resistant bacterial strains, including mycobacteria by evading common mechanisms of resistance and exerting novel mechanisms of action. A variety of novel and structurally diverse AAGs have been synthesised within this study providing lead structures with promising activity for the development of antimicrobial agents. A series of AAGs synthesised from the scaffolds of amikacin, kanamycin and neomycin were synthesised by conjugation of several hydrophobic groups to the AG scaffold. Derivatives were prepared by utilizing either the active functionality from the sulfonylacetamides conjugated via amide or triazole linkers; or by an alternative prodrug-based strategy utilizing long alkyl chains conjugated via ester linkages. Due to AGs broad-spectrum antibacterial activities, these compounds were evaluated for their antimicrobial inhibitory effect towards M. tuberculosis and S. aureus. Several structures were identified to display potent antitubercular activities. One of the kanamycin-based prodrugs was found to exert an increased antitubercular activity in comparison to the parent scaffold (MIC90 3 μg/mL), while amikacin derivatives maintained significant inhibitory effect (MIC90 3 – 6 μg/mL). The most active AAG utilizing the active functionality of the sulfonylacetamides was an amide-linked conjugate of amikacin (MIC90 22 μg/mL).
Intracellular infections from bacterial pathogens such as M. tuberculosis are the causative agents of several serious diseases worldwide. Although the mononuclear phagocyte system primarily consists of macrophages, and constitutes the primary line of defence against infections, several bacterial pathogens have evolved the ability to survive and reproduce within intracellular host organelles. Intracellular infections are difficult to eradicate through traditional chemotherapeutic approaches due to the poor intracellular penetration of antibiotics. Moreover, the resulting low intracellular concentration of antibiotics is often ineffective against intracellular pathogens and furthermore promotes the development of drug resistance. Consequently, novel approaches to improve therapeutic effectiveness must be considered to advance treatment towards persistent intracellular bacterial infections. Nanoparticle-based drug delivery systems are one such approach; enabling improved antibiotic bioavailability and targeted site-specific drug delivery, offering the ability to overcome the less than desirable effects most antibiotics display towards intracellular pathogens. Liposomal drug delivery vectors are the most established and investigated nanocarriers, offering nontoxic biological delivery systems that can enhance the antimicrobial efficiency and therapeutic index of various chemotherapeutics.
Liposomes provide unique delivery systems for antibiotics, such as AGs, as they can enhance efficiency whilst decreasing toxicity. Liposomal encapsulated AGs have demonstrated enhanced bactericidal activity towards intracellular infections in vitro and in vivo. Liposomal encapsulated amikacin has demonstrated its effectiveness in clinical trials and is currently FDA approved for the treatment of Mycobacterium avium complex. Within this study, amphiphilic-based prodrug derivatives of amikacin and mannosylated targeting ligands were utilized to formulate novel liposomal preparations for the treatment of pulmonary infections. Amphiphilic derivatization of amikacin allowed passive drug loading of the active therapeutic within the lipid bilayer, providing improved drug loading capacities compared to conventional approaches of loading amikacin within the aqueous core. Additionally, incorporation of the therapeutic AAG within the bilayer resulted in vesicles with improved membrane stability and more desirable physiochemical properties compared to conventional formulations. To test these liposomal formulations as a delivery system against intracellular pathogens in vitro, a murine macrophage cell line expressing mannose receptor (RAW264.7) was infected with S. aureus and bacterial inhibition was determined. All formulations displayed concentration-dependent killing efficiencies, while some were capable of complete intracellular bacterial inhibition at higher concentrations. The lipid derivatized amikacin-based prodrug delivery systems provide a novel liposomal delivery platform for intracellular infections, whilst offering the potential to overcome the shortcomings of current liposomal formulations such as poor stability and drug leakage. Once realized, this application could improve treatment towards serious intracellular pulmonary infections such as M. tuberculosis.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
Institute for Glycomics
Griffith Health
Full Text
43
Johnston, Alexander Henderson. „Novel approaches to dendrimer based radiopharmaceutical imaging agents and drug delivery systems“. Thesis, University of Southampton, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.582662.
Der volle Inhalt der QuelleAnnotation:
The work reported in this thesis details two novel approaches towards the use of poly(amidoamine) (PAMAM) dendrimers for medicinal applications. The introduction contains a brief overview on the synthesis and properties of dendrimers, focusing in particular on PAMAM dendrimers and the growing interest in their use as polymer therapeutics. The second part of the introduction contains an overview of the role of Tc99m in nuclear medicine. The final part of the introduction gives an explanation of the genetic disorder, cystic fibrosis, concentrating on the degenerative lung disease associated with the disease and the role neutrophil elastase has in the degeneration of the lung. The next chapter then proceeds to describe the preparation of 4th and 5th generation PAMAM dendrimers with dioctylamine surface groups. These surface modified dendrimers are reported as potential NaTc99m04 complexation systems for potential application as radiopharmaceutical agents for use in lung imaging. The next chapter describes the preparation of PAMAM dendrimers with p-lactam and saccharine-based inhibitors linked to the surface. These modified dendrimers are shown to inhibit intracellular neutrophil elastase in samples of human blood. The results indicate that the modified dendrimers could potentially be used to reduce the extent of lung damage in a cystic fibrosis patient and improve both their quality of life and life expectancy.
44
MURA, CARLA. „Preparation, development and evaluation of novel drug delivery systems for colon targeting“. Doctoral thesis, Università degli Studi di Cagliari, 2011. http://hdl.handle.net/11584/266294.
Der volle Inhalt der QuelleAnnotation:
Il direzionamento di farmaci al colon sta assumendo un ruolo sempre più importante non solo per il targeting di farmaci usati nel trattamento di patologie del colon ma anche come sito per l’assorbimento e raggiungimento sistemico di proteine. Lo scopo di questo lavoro è stato quello di preparare diversi sistemi per il direzionamento al colon di due farmaci modello usati nel trattamento di patologie del colon: l’acido 5-amminosalicilico (5-ASA) e il metronidazolo (MTZ). Per la preparazione di questi sistemi sono stati scelti sistemi pH-dipendent ed enzima-dipendenti. Sistemi pH-dipendenti sono stati preparati con il 5-ASA. N-Succinyl-chitosano (SucCH) è stato usato come carrier grazie alle sue favorevoli proprietà per il direzionamento al colon. Sono stati preparati vari sistemi matriciali con il 5-ASA, chitosano e N-Succinyl-chitosano con e senza ciclodestrina, con lo scopo di valutare l’influenza della presenza della ciclodestrina nelle varie formulazioni. Infine sono state preparate microparticelle di 5-ASA e SucCH. Tutti i sistemi sono stati caratterizzati e sono stati effettuati studi di rigonfiamento e di rilascio, studi di mucoadesione e studi in vivo usando il modello di colite indotta da TNBS in ratti. Sistemi enzima-dipendenti sono stati preparati con il metronidazolo attraverso la sintesi di profarmaci del MTZ, legando covalentemente il farmaco alla α-, β- e γ-ciclodestrina e al chitosano. Tutti i profarmaci sono stati caratterizzati e sono stati effettuati studi di stabilità in vitro e studi di rilascio del farmaco ex vivo con il contenuto del cieco e del colon di ratti.
----------------------------------------------------------------------------------------------------------------------------Colon specific drug delivery has gained increased importance not only for drug delivery in the treatment of local colonic diseases but also as potential site for the systemic delivery of therapeutic peptides and proteins. The aim of this work was to develop different colon specific delivery systems by using two model drugs for the treatment of colon diseases: 5-aminosalicylic acid (5-ASA) and metronidazole (MTZ). Two different types of colon drug delivery systems were chosen: enzyme-dependent system and pH-dependent system. Different 5-ASA pH-dependent systems were developed for the treatment of IBD. N-Succinyl-chitosan was chosen as carrier system because it presents favorable properties for the delivery of drugs to the colon. 5-ASA loaded N-Succinyl-chitosan and chitosan matrices were prepared. β-cyclodextrin (CD) were loaded into the polymers and the influence of CD on the system characteristics was studied. 5-ASA loaded N-Succinyl-chitosan microparticles were also prepared. These systems were chemically and analytically characterized; in vitro swelling and release studies were performed, finally mucodhesion and in vivo studies using TNBS colitis rat model were carried out. Macromolecular prodrugs of MTZ and α-, β- and γ-cyclodextrin or chitosan (CHT) were prepared by linking the drug with a covalent bond to the macromolecule (CD or CHT). All the prodrugs were chemically and analytically characterized. In vitro stability and ex vivo release studies were performed to investigate their usefulness as colon delivery systems.
45
Nahak, Prasant. „Physicochemical studies on lipidic components with special reference to monolayer, bilayer,and solid lipid nanoparticle“. Thesis, University of North Bengal, 2017. http://ir.nbu.ac.in/handle/123456789/3967.
Der volle Inhalt der Quelle
46
Gunji, Shutaro. „A novel drug delivery system of intraperitoneal chemotherapy for peritoneal carcinomatosis using gelatin microspheres incorporating cisplatin“. Kyoto University, 2013. http://hdl.handle.net/2433/180608.
Der volle Inhalt der Quelle
47
Esfand, Roseita. „Synthesis and characterisation of dendrimer-drug complexes and evaluation of dendrimeric compounds as novel drug delivery systems“. Thesis, University of Kent, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241934.
Der volle Inhalt der Quelle
48
Colby, Aaron Henry. „Novel drug delivery systems: pH-responsive expansile nanoparticles & drug concentrating devices as tools for treating cancer“. Thesis, Boston University, 2014. https://hdl.handle.net/2144/12957.
Der volle Inhalt der QuelleAnnotation:
Thesis (Ph.D.)--Boston UniversityNew strategies for treatment and methods of drug delivery are required for patients suffering from cancer-the second leading cause of death worldwide. Current chemotherapeutic treatments frequently suffer from poor water solubility, systemic toxicity, poor accumulation within the target tissues and an inability to eradicate all remaining tumor following resection procedures. Nanoparticles (NPs) are extensively investigated as a means to increase drug solubility, alter biodistribution, target specific sites within the body, and minimize drug side effects and, as such, numerous NP formulations are being investigated as drug delivery devices to assist in the treatment and management of cancer. We have developed a pH-responsive expansile nanoparticle (eNP) that can encapsulate the hydrophobic chemotherapeutic agent Paclitaxel (Pax) (a poorly water soluble, yet potent chemotherapeutic agent), and deliver it specifically to the intracellular compartment of tumor cells. Paclitaxel-loaded-eNPs (Pax-eNPs) localize specifically to regions of intraperitoneal (IP) tumors and, once taken up by tumor cells, undergo a conformational change upon exposure to the mildly acidic cellular endosome that results in eNP swelling and intratumoral drug release. In this work, we describe: 1) the clinical problem and cost (both humanitarian and fmancial) of local cancer recurrence following tumor resection; 2) the eNP delivery system and, specifically, we characterize the swelling of eNPs using microscopy and tunable resistive pulse sensing techniques; 3) the in vitro activity of Pax-eNPs in breast cancer cells; 4) the improved efficacy of Pax- eNPs compared to the standard clinical formulation of Pax (i.e., Pax dissolved in Cremophor/Ethanol) in a murine model of established peritoneal mesothelioma; and, 5) the ability of eNPs to act as intratumoral, intracellular drug concentrating devices. Further investigation of this NP-based drug delivery system will facilitate a greater understanding of the materials and devices used in the delivery of chemotherapeutic agents and may lead to the clinical translation and application of eNPs.
49
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.
Der volle Inhalt der Quelle
50
Wehrung, Daniel. „Development and Evaluation of Novel Light-Responsive Drug Delivery Systems from Alkoxyphenacyl Polycarbonates“. NEOMED Integrated Pharmaceutical Medicine / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ne2mh1441828458.
Der volle Inhalt der Quelle