Spelling suggestions: "subject:"drug delivery atemsystem"" "subject:"drug delivery systsystem""
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Transdermal delivery of 5-Fluorouracil with PheroidTM technology / C.P. van DykVan Dyk, Christina Petronella January 2008 (has links)
5-Fluorouracil (5FU) is a pyrimidine analogue, indicated for the therapy of proliferative skin diseases such as actinic keratosis (AK), superficial basal cell carcinoma and psoriasis. It has also been used for the treatment of solid tumours like colorectal, breast and liver carcinomas for nearly 40 years.
Although 5FU has always been administered parenterally and orally, metabolism is rapid and absorption is erratic. Several severe side-effects are also commonly associated with 5FU therapy, including myelosuppression, hand-foot syndrome and gastrointestinal effects. Seeing that 5FU is an important part of the treatment of several malignant and pre-malignant disorders, it would be advantageous to find a delivery route and delivery system that negate absorption and metabolic variation and decrease side-effects.
The transdermal route provides a promising alternative to the above-mentioned conventional delivery routes, solving most of the problems associated with parenteral and oral administration. That being said, the formidable barrier situated in the skin is not easily breached. The stratum corneum, the outermost skin layer, is mostly lipophilic in nature, preventing hydrophilic molecules such as 5FU from entering.
5FU-containing creams and lotions are currently commercially available, but absorption is still very limited. The transdermal absorption from these formulations has been compared to that obtained with the use of new transdermal delivery vehicles, with the newer formulations proving to be promising.
It was decided to entrap 5FU in a novel therapeutic system, in the form of the Pheroid™ system, to increase its transdermal penetration.
Pheroid™ vesicles are stable spherical structures in a unique, emulsion-like formulation, and fall in the submicron range. The main components of the Pheroid™ system are the ethyl esters of the essential fatty acids linoleic acid and linolenic acid, as well as the cys-form of oleic acid, and water. The formulation is saturated with nitrous oxide (N20).
Although Pheroid™ vesicles may resemble other lipid-based vehicles, such as liposomes and micro-emulsions, they are unique in the sense that they have inherent therapeutic qualities as well. The Pheroid™ formulation can be specifically manipulated to yield different types of vesicles, ensuring a fast transport rate, high entrapment efficiency, rapid delivery and stability of the delivery system for a specific drug.
In this study, 5FU was entrapped in the Pheroid™ formulation. Transdermal permeation studies were then performed to evaluate the influence of this delivery system on the transdermal flux of 5FU.
Vertical Franz diffusion cells were utilised to determine the transdermal penetration of 5FU. Only Caucasian female abdominal skin was used to minimise physiological variables. Diffusion studies were done over 12 hour periods, with the entire receptor phase being withdrawn at predetermined intervals. Samples were analysed using high performance liquid chromatography (HPLC), after which the cumulative concentration of active was plotted against time. The linear portion of this graph represents the flux of 5FU through the skin.
It was found that there were differences in the results between formulations containing 5FU in a phosphate buffer solution (PBS)-based Pheroid™ and water-based Pheroid™, though the difference was not statistically significant. The 0.5 % 5FU in water-based Pheroid™ resulted in a significantly bigger yield than the control (1 % 5FU in water) as well as a significant difference to the 1 % 5FU in PBS-based Pheroid™ formulation. In general the water-based Pheroid™ formulations had greater average cumulative concentrations, yields and fluxes than the other formulations.
The fluxes obtained with the water-based Pheroid™ formulations also correlated well with a previous study done by Kilian (2004).
Thus it can be concluded that the Pheroid™ therapeutic delivery system enhances the transdermal penetration of 5FU. Water-based Pheroid™ formulations proved to be more effective than PBS-based Pheroid™ formulations. It can also be concluded that a 0.5 % 5FU in water-based Pheroid™ formulation can be used instead of a 1 % formulation, because there were no statistically significant differences between the two formulations. This would be advantageous - patient compliance can be enhanced because of a more tolerable formulation with fewer side effects, while manufacturing cost is lowered by using a lower concentration of active.
It is recommended that some aspects of the study be investigated further to optimise the transdermal delivery of 5FU using the Pheroid™ therapeutic system. These aspects
include optimising the composition of the Pheroid formulation, investigating the entrapment process of 5FU within Pheroid™ spheres, the influence of PBS and water as basis of the Pheroid™ formulation and the amount of 5FU remaining in the epidermis after the 12 hour period of the diffusion study.
Keywords: 5-Fluorouracil, Franz diffusion cell, Heat separated epidermis, Skin penetration, Transdermal, Drug delivery system, Pheroid™ / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2008.
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Triple Fortification of Salt with Vitamin A, Self-emulsifying Drug Delivery System, Iron, and IodineKwan, Lana 23 July 2012 (has links)
Triple fortification of salt with vitamin A, iron, and iodine has been investigated in the past to reduce micronutrient deficiencies in the developing world.
The objective is to develop integrated nutrient delivery technology by microencapsulating a self-emulsifying drug delivery system (SEDDS) made of surfactants and a bioactive compound, retinyl palmitate. The SEDDS is used to enhance absorption of the vitamin A through food systems and to achieve targeted release of the active ingredient.
Encapsulating vitamin A was difficult when using the spray dryer and the enteric coating, Aquacoat®. Losses of the micronutrient after a three month storage period ranged from 50-99% at both 25°C/20% RH and 45°C/60% RH. The result of a matrix encapsulation and poor coating formation contributed to the high losses.
Further investigation of coating systems with the aim of stabilizing all three samples for a six month storage period such as using other encapsulating methods is recommended.
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Triple Fortification of Salt with Vitamin A, Self-emulsifying Drug Delivery System, Iron, and IodineKwan, Lana 23 July 2012 (has links)
Triple fortification of salt with vitamin A, iron, and iodine has been investigated in the past to reduce micronutrient deficiencies in the developing world.
The objective is to develop integrated nutrient delivery technology by microencapsulating a self-emulsifying drug delivery system (SEDDS) made of surfactants and a bioactive compound, retinyl palmitate. The SEDDS is used to enhance absorption of the vitamin A through food systems and to achieve targeted release of the active ingredient.
Encapsulating vitamin A was difficult when using the spray dryer and the enteric coating, Aquacoat®. Losses of the micronutrient after a three month storage period ranged from 50-99% at both 25°C/20% RH and 45°C/60% RH. The result of a matrix encapsulation and poor coating formation contributed to the high losses.
Further investigation of coating systems with the aim of stabilizing all three samples for a six month storage period such as using other encapsulating methods is recommended.
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Cimentos ósseos alfa-fosfato tricálcico e alfa fosfato tricálcico de dupla pega : desenvolvimento/caracterização para fins de liberação controlada de fármacos e vigilância sanitáriaSilveira, Julio Cesar Colpo da January 2017 (has links)
A ortopedia e a odontologia têm especial interesse às tecnologias biocompatíveis que apresentam a fase alfa do fosfato tricálcico (α-TCP), pois estas são capazes de formar hidroxiapatita deficiente em cálcio, similar à óssea. Porém, a baixa resistência mecânica limita sua aplicação. A fim de superar essa limitação, foi agregada acrilamida ao cimento α-TCP, com redutor de líquido, originando o cimento α-TCP de dupla pega. A partir disso foram desenvolvidos compostos à base de cimento de α-TCP e α-TCP de dupla pega agregados dos fármacos sulfato de gentamicina, cloridratos de lidocaína, bupivacaína e levobupivacaína e testada sua funcionalidade como sistemas de liberação de fármacos. Não existem dados bibliográficos sobre liberação de fármacos por sistemas de cimento α-TCP de dupla pega. A metodologia utilizada foi qualiquantitativa. Para as diferenças analíticas considerou-se o intervalo de confiança de 95% com nível de significância menor que 5% (p<0,05). O estudo compreendeu três fases. Na Fase 1 foram elaborados corpos de prova à base de cimento α-TCP e α-TCP de dupla pega com e sem (grupo-controle) adição de fármacos. Na Fase 2 os biomateriais estudados foram caracterizados por difração de raios X, espectroscopia de absorção no infravermelho com transformada de Fourier, microscopia eletrônica de varredura, resistência mecânica a compressão axial, densidade, porosidade e absorção de líquido; sendo também proposta a análise da porosidade por meio de imagens. A Fase 3 corresponde ao estudo da cinética da liberação dos fármacos in vitro, onde os corpos de prova foram imersos em solução tampão fosfato pH 7,0 e as amostras analisadas por meio de UV-vis. A liberação do antibiótico também foi avaliada por Espectroscopia de Impedância Eletroquímica (EIS), como proposta inovadora. Conforme os resultados, ambos os cimentos funcionaram como sistemas de liberação dos fármacos. Tanto o sistema hidrogel, quanto os fármacos não modificaram as propriedades estruturais do cimento. O sistema com hidrogel apresentou melhor resistência mecânica. A difusão Fickiana foi o principal mecanismo envolvido no processo de liberação dos fármacos, com menor influência do relaxamento das cadeias. A técnica de EIS mostrou-se promissora para avaliação de liberação de fármacos. / To better regulate it is necessary to know the new Technologies. Orthopedics and dentistry have demonstrated special interest in biocompatible technologies that present the alpha phase of tricalcium phosphate (α-TCP), whit can form calcium-deficient hydroxyapatite (like bone hydroxyapatite). However, its application is limited by the low mechanical resistance. To overcome this limitation, acrylic hydrogel containing liquid reducer was added to the α-TCP cement, resulting in the α-TCP double setting cement. From this, composites of α-TCP and α-TCP double setting cements aggregates of the drugs gentamicin sulfate, lidocaine, bupivacaine and levobupivacaine hydrochlorides were developed and the functionality drug delivery systems was tested. There isn't bibliographic data about drugs release systems by α-TCP double setting cement. Qualitative and quantitative methodologies were applied. For the analytical differences, we considered the 95% confidence interval with a level of significance lower than 5% (p <0.05). It comprised three different phases. In Phase 1, an α-TCP and α-TCP double setting cement specimens were prepared with and without (control group) drugs addition. In Phase 2, the studied biomaterials were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, compression mechanical resistance, density, porosity and liquid absorption, being also proposed of the porosity analysis by images. The Phase 3 corresponds to the study of the in vitro drug release kinetics. The specimens were immersed in phosphate buffer solution pH 7.0 and the samples analyzed by UV-vis. As an innovative proposal, drug release was also assessed using Electrochemical Impedance Spectroscopy (EIS). According to the results, both cements functioned as controlled drug delivery systems. The hydrogel improved the properties of cement moreover the drugs did not impair these properties. Fick diffusion was the main mechanism involved in the process of drug release by composites, with a minor influence of polymer chain relaxation. The EIS technique proved to be promising for the evaluation of drug release.
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Cimentos ósseos alfa-fosfato tricálcico e alfa fosfato tricálcico de dupla pega : desenvolvimento/caracterização para fins de liberação controlada de fármacos e vigilância sanitáriaSilveira, Julio Cesar Colpo da January 2017 (has links)
A ortopedia e a odontologia têm especial interesse às tecnologias biocompatíveis que apresentam a fase alfa do fosfato tricálcico (α-TCP), pois estas são capazes de formar hidroxiapatita deficiente em cálcio, similar à óssea. Porém, a baixa resistência mecânica limita sua aplicação. A fim de superar essa limitação, foi agregada acrilamida ao cimento α-TCP, com redutor de líquido, originando o cimento α-TCP de dupla pega. A partir disso foram desenvolvidos compostos à base de cimento de α-TCP e α-TCP de dupla pega agregados dos fármacos sulfato de gentamicina, cloridratos de lidocaína, bupivacaína e levobupivacaína e testada sua funcionalidade como sistemas de liberação de fármacos. Não existem dados bibliográficos sobre liberação de fármacos por sistemas de cimento α-TCP de dupla pega. A metodologia utilizada foi qualiquantitativa. Para as diferenças analíticas considerou-se o intervalo de confiança de 95% com nível de significância menor que 5% (p<0,05). O estudo compreendeu três fases. Na Fase 1 foram elaborados corpos de prova à base de cimento α-TCP e α-TCP de dupla pega com e sem (grupo-controle) adição de fármacos. Na Fase 2 os biomateriais estudados foram caracterizados por difração de raios X, espectroscopia de absorção no infravermelho com transformada de Fourier, microscopia eletrônica de varredura, resistência mecânica a compressão axial, densidade, porosidade e absorção de líquido; sendo também proposta a análise da porosidade por meio de imagens. A Fase 3 corresponde ao estudo da cinética da liberação dos fármacos in vitro, onde os corpos de prova foram imersos em solução tampão fosfato pH 7,0 e as amostras analisadas por meio de UV-vis. A liberação do antibiótico também foi avaliada por Espectroscopia de Impedância Eletroquímica (EIS), como proposta inovadora. Conforme os resultados, ambos os cimentos funcionaram como sistemas de liberação dos fármacos. Tanto o sistema hidrogel, quanto os fármacos não modificaram as propriedades estruturais do cimento. O sistema com hidrogel apresentou melhor resistência mecânica. A difusão Fickiana foi o principal mecanismo envolvido no processo de liberação dos fármacos, com menor influência do relaxamento das cadeias. A técnica de EIS mostrou-se promissora para avaliação de liberação de fármacos. / To better regulate it is necessary to know the new Technologies. Orthopedics and dentistry have demonstrated special interest in biocompatible technologies that present the alpha phase of tricalcium phosphate (α-TCP), whit can form calcium-deficient hydroxyapatite (like bone hydroxyapatite). However, its application is limited by the low mechanical resistance. To overcome this limitation, acrylic hydrogel containing liquid reducer was added to the α-TCP cement, resulting in the α-TCP double setting cement. From this, composites of α-TCP and α-TCP double setting cements aggregates of the drugs gentamicin sulfate, lidocaine, bupivacaine and levobupivacaine hydrochlorides were developed and the functionality drug delivery systems was tested. There isn't bibliographic data about drugs release systems by α-TCP double setting cement. Qualitative and quantitative methodologies were applied. For the analytical differences, we considered the 95% confidence interval with a level of significance lower than 5% (p <0.05). It comprised three different phases. In Phase 1, an α-TCP and α-TCP double setting cement specimens were prepared with and without (control group) drugs addition. In Phase 2, the studied biomaterials were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, compression mechanical resistance, density, porosity and liquid absorption, being also proposed of the porosity analysis by images. The Phase 3 corresponds to the study of the in vitro drug release kinetics. The specimens were immersed in phosphate buffer solution pH 7.0 and the samples analyzed by UV-vis. As an innovative proposal, drug release was also assessed using Electrochemical Impedance Spectroscopy (EIS). According to the results, both cements functioned as controlled drug delivery systems. The hydrogel improved the properties of cement moreover the drugs did not impair these properties. Fick diffusion was the main mechanism involved in the process of drug release by composites, with a minor influence of polymer chain relaxation. The EIS technique proved to be promising for the evaluation of drug release.
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Desenvolvimento de sistemas de liberação prologando do antirretroviral zidovudina a partir de hidróxido duplo lamelarAGUILERA, Cindy Siqueira Britto 29 July 2016 (has links)
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Previous issue date: 2016-07-29 / CAPES / Os hidróxidos duplos lamelares (HDL) vêm recebendo grande atenção no
desenvolvimento de sistemas de liberação de fármacos, devido à capacidade que
esses sólidos inorgânicos apresentam, de intercalar na sua região interlamelar, ou
adsorver em sua vasta área superficial, substâncias biologicamente ativas. Os HDL
podem ser sintetizados em laboratório por rotas simples e de baixo custo, que
permitem o isolamento de sólidos de alta pureza. O antirretroviral zidovudina (AZT)
apresenta, como principal limitação, o baixo tempo de meia vida plasmática, sendo
necessária a administração de várias doses diárias, e assim favorecendo o surgimento
de reações adversas. Nesse contexto, o presente trabalho teve como objetivo o
desenvolvimento de sistema de liberação prolongada para o fármaco AZT, utilizando
o HDL como carreador. Para isso, foi realizado, a síntese e caracterização de MgAlCl-HDL,
e obtenção de sistemas HDL:AZT, através da síntese direta por
copreciptação, realizando variações na concentração de AZT no meio reacional e no
tempo de agitação durante a síntese. Os materiais obtidos foram caracterizados pelas
técnicas de difração de raios-X (DRX), termogravimetria (TG), análise térmica
diferencial (DTA), espectroscopia no infravermelho (IV), microscopia eletrônica de
varredura (MEV), análises de tamanho de partícula, porosidade e área superficial,
além da análise elementar de metais e de carbono, hidrogênio e nitrogênio (CHN).
Entre os sistemas HDL:AZT, o obtido com proporção molar 1:1 (Al+3/AZT) no meio
reacional e 1 hora de agitação, apresentou o melhor perfil de liberação prolongada do
fármaco, alcançando 90% de liberação do AZT em 24 horas de estudo. O MgAl-ClHDL
demonstrou ser um carreador biocompatível, além de proporcionar uma
diminuição na citotoxicidade do AZT frente a linhagem de macrófagos humanos. Desta
forma, o sistema de liberação prolongada obtido, para o fármaco AZT, poderá ser
utilizado em formulações farmacêuticas, no intuito de otimizar a terapia antirretroviral
atual. / Layered double hydroxides (LDH) have received great attention in the development of
drug delivery systems because of the ability these inorganic solids present to
intercalate in its interlayer region, or adsorb on its vast surface area, biologically active
substances. The LDH can be synthesized in the laboratory by simple and low-cost
routes that generate high-purity solids. The antiretroviral zidovudine (AZT) has as its
main limitation, low plasma half-life, requiring the administration of multiple daily doses,
and thus favoring the appearance of side effects. In this context, the present study
aimed to develop sustained release systems for the AZT using LDH as a drug carrier.
In order to accomplish this goal, it was carried out the synthesis and characterization
of the MgAl-Cl-LDH and obtained the systems LDH:AZT by coprecipitation, with
variations of AZT concentration in the reactional medium and stirring time during
synthesis. The materials were characterized by the following techniques: X-ray
diffraction (XRD), Thermogravimetry (TG), Differential Thermal Analysis (DTA),
Infrared Spectroscopy (IR), Scanning Electron Microscopy (SEM), Particle Size
Analysis, Porosity and Surface Area, and Elemental Analysis of Metals and Carbon,
Hydrogen and Nitrogen (CHN). Among the LDH:AZT systems, the one with molar ratio
1:1 (Al+3/AZT) in the reaction medium and one hour of stirring presented the best
sustained drug release profile, reaching the amount of 90% of AZT released within 24
hours of study. The MgAl-Cl-LDH showed to be a biocompatible drug carrier, in
addition to providing a decrease in cytotoxicity of AZT against human macrophage
lineage cells. Therefore, the sustained release system obtained to AZT may be used
in pharmaceutical formulations in order to optimize the current antiretroviral therapy.
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A therapeutic angiogenesis of sustained release of basic fibroblast growth factor using biodegradable gelatin hydrogel sheets in a canine chronic myocardial infarction model / 慢性心筋梗塞大動物モデルに対するbFGF徐放化ゼラチンハイドロゲルシートを用いた血管新生療法Motoyuki, Kumagai 25 November 2019 (has links)
京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13290号 / 論医博第2188号 / 新制||医||1039(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 山下 潤, 教授 木村 剛, 教授 浅野 雅秀 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM
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Identification of a Peptide Sequence That Improves Transport of Macromolecules Across the Intestinal Mucosal Barrier Targeting Goblet CellsKang, Sang, Woo, Jung Hee, Kim, Min Kook, Woo, Sang Soo, Choi, Jin Hyuk, Lee, Hong Gu, Lee, Nam Kyung, Choi, Yun Jaie 01 June 2008 (has links)
In this study, we demonstrated that the CSKSSDYQC-peptide ligand which was identified from a random phage-peptide library through an in vivo phage display technique with rats could prominently improve the transport efficiency of macromolecules, such as large filamentous phage particles (M13 bacteriophage), across the intestinal mucosal barrier. Synthetic CSKSSDYQC-peptide ligands significantly inhibited the binding of phage P1 encoding CSKSSDYQC-peptide ligands to the intestinal mucosal tissue and immunohistochemical analysis showed that the CSKSSDYQC-peptide ligands could be transported across the intestinal mucosal barrier via goblet cells as their specific gateway. Thus, we inferred that CSKSSDYQC-peptide ligand might have a specific receptor on the goblet cells and transported from intestinal lumen to systemic circulation by transcytosis mechanism. These results suggest that CSKSSDYQC-ligand could be a promising tool for development of an efficient oral delivery system for macromolecular therapeutics in the carrier-drug conjugate strategy.
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Development of Engineered Extracellular Vesicle-Liposome Hybrid Using Baculovirus-Expression System / バキュロウイルス発現系を用いて機能化された細胞外ベシクル-リポソームハイブリッドの開発Ishikawa, Raga 23 March 2021 (has links)
京都大学 / 新制・課程博士 / 博士(工学) / 甲第23225号 / 工博第4869号 / 新制||工||1760(附属図書館) / 京都大学大学院工学研究科高分子化学専攻 / (主査)教授 秋吉 一成, 教授 跡見 晴幸, 教授 大塚 浩二 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM
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Precise Structural and Functional Control of Molecular Assemblies Composed of Amphiphilic Peptides Having a Hydrophobic Helical Block / 疎水性ヘリックスをもつ両親媒性ペプチド分子集合体の構造および機能の精密制御Uesaka, Akihiro 23 March 2015 (has links)
京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第18949号 / 工博第3991号 / 新制||工||1615(附属図書館) / 31900 / 京都大学大学院工学研究科材料化学専攻 / (主査)教授 木村 俊作, 教授 瀧川 敏算, 教授 秋吉 一成 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM
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