No description available.

No description available.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 6 uppsatser.

Adenosine is currently limited in its application as a treatment for various cancers since intravenous infusion has not been successful due to enzymatic degradation. Entrapment/association of adenosine into chitosan nanoparticles offers a possible solution to this problem. Chitosan nanoparticles which are formed by ionotropic gelation. The size, zeta potential, morphology, entrapment efficiency, and in vitro drug release were investigated. In the swollen state, nanoparticle had an average size between 425 to 515 nm and a positive zeta potential, as measured by dynamic light scattering. Particle size measured by transition electron microscopy varied between 135 to 183 nm. Average entrapment efficiency in the range of 72 to 78% was achieved depending on initial adenosine loading and an average association efficiency of 84%. Release studies show that more than 98% of the adenosine remained entrapped/associated with the chitosan nanoparticles for at least 120 hours in PBS (pH 7.4).

No description available.

No description available.

Despite the great success of hip implant surgeries, wear particle-induced implant aseptic loosening still limits the implant longevity. Simvastatin, an FDA-approved cholesterol lowering statin, is a promising drug candidate for the treatment of implant aseptic loosening due to its anti-inflammatory properties as well as its ability to stimulate bone growth and inhibit bone resorption. In addition, alginate microspheres have been used extensively in drug delivery applications because of alginate properties, including biocompatibility and gelation in mild conditions. However, the hydrophobicity of simvastatin, as well as the large alginate microsphere pore size leading to the leakage of low molecular weight drugs are limiting factors for their use as a delivery system for simvastatin. Therefore, the objectives of this thesis were twofold: 1. To complex simvastatin with 2-hydroxypropyl-β-cyclodextrin (HP-βCD) in order to increase its solubility; and 2. To increase simvastatin encapsulation efficiency in alginate microspheres by coating the microspheres with chitosan, adding dextran sulfate in the alginate solution, and optimizing the gelation conditions used for the synthesis of the microspheres (e.g., volume of gelation medium, curing time, and addition of simvastatin in the gelation medium). Results showed that simvastatin complexation with HP-βCD increased with HP-βCD to simvastatin molar ratio, to a maximum of 97.6% at the molar ratio of 10. Results also showed that chitosan coating of the alginate microspheres increased simvastatin encapsulation efficiency (up to 10.6%), which was further improved (up to 14.0%) when adding 2.0% (w/v) dextran sulfate to the alginate solution. This increase was likely due to electrostatic interactions between dextran sulfate and chitosan in addition to alginate, resulting in a denser coating. Finally, the addition of simvastatin in the gelation medium was shown to also increase simvastatin encapsulation (up to 22.4%), likely because of a decrease in the diffusion of simvastatin out of the microspheres. Overall, this work completed the initial steps for the development of an alginate-based drug delivery system for simvastatin with the long-term goal of providing a local delivery of simvastatin to modulate implant aseptic loosening.

京都大学 / 新制・課程博士 / 博士(工学) / 甲第23161号 / 工博第4805号 / 新制||工||1751(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 田畑 泰彦, 教授 秋吉 一成, 教授 沼田 圭司 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

Considerando que a obtenção de uma formulação farmacêutica pode ser melhor planejada se algumas condições biológicas inerentes à cavidade oral forem contempladas e que os sistemas de liberação modificada podem ser ferramentas para o controle de doenças orais, o objetivo do trabalho é obter uma formulação contendo clorexidina, avaliando seu efeito sobre os mesmos. Este trabalho foi dividido em duas etapas, sendo que a primeira envolveu a obtenção da formulação mais adequada aos experimentos biológicos e a segunda avaliou seus efeitos sobre biofilmes patogênicos orais. Assim, formulações com diferentes concentrações de clorexidina foram preparadas e avaliadas visualmente em relação à sua integridade física nas condições de crescimento dos biofilmes, seguido de ensaio de liberação em meio estático utilizando tampão como meio de dissolução (meio de dissolução convencional). A formulação selecionada foi submetida a ensaios de liberação em meio estático contendo os diferentes caldos de cultura bacterianos como meio de dissolução. Na segunda etapa do trabalho, o efeito da formulação selecionada foi avaliado em biofilmes cariogênicos de Streptococcus mutans ou biofilmes periodontopatogênicos de Porphyromonas gingivalis. Biofilmes de S. mutans (n=6) ou P. gingivalis (n=3) foram formados em caldos de cultura sob lâminas de vidro por 6 e 3 dias, respectivamente, sendo expostos a um dos seguintes tratamentos: 1) Formulação contendo 92% de quitosana e 8% de hidroxipropil metilcelulose (CV, como controle do veículo) ou 2) Formulação contendo 82% de quitosana, 8% de hidroxipropil metilcelulose e 10% de clorexidina (CHX, grupo experimental). Um grupo sem exposição à formulação foi incluído como controle negativo (CN). Após o período experimental, a viabilidade bacteriana, o pH dos biofilmes e a quantificação de clorexidina liberada para os caldos de cultura foram determinados. Os dados foram analisados estatisticamente por teste de Tukey-Kramer e Tukey, sendo o nível de significância estabelecido em 5%. Os resultados sugerem que ainda que a liberação de clorexidina da formulação nos caldos de cultura de S. mutans e P. gingivalis tenha sido menor se comparada ao meio de dissolução convencional (p<0,05), o efeito biológico promovido foi observado para ambos os biofilmes. Para o pH dos biofilmes de S. mutans, os grupos CN e CV não apresentaram diferença entre si (p>0,05), mas apresentaram quedas de pH maiores se comparados à CHX (p<0,05). CHX também resultou em menor viabilidade bacteriana dos biofilmes se comparada aos controles (p<0,05), que não apresentaram diferença entre si (p>0,05). Para P. gingivalis também houve mais morte celular nos biofilmes expostos à CHX (p<0,05) mas CV também apresentou perda de viabilidade em comparação à CN (p<0,05). Apesar da liberação de clorexidina da formulação ter sido dificultada pela presença dos microrganismos, os resultados sugerem que o sistema de liberação obtido foi capaz de diminuir a patogenicidade dos biofimes de Streptococcus mutans e de Porphyromonas gingivalis. Assim, o presente estudo sugere a importância de aliar os estudos de diferentes áreas de conhecimento de forma a contribuir no planejamento das formulações, vislumbrando futuros benefícios clínicos para o controle das doenças orais. / Considering that obtaining a pharmaceutical formulation can be better planned if some biological conditions inherent to the oral cavity are contemplated and that the modified release systems may be tools for the control of oral diseases, the aim of the work is to obtain a formulation containing chlorhexidine and evaluate its effect in pathogenic biofilms. This work was divided in two stages, the first involved obtaining the most appropriate formulation for biological experiments and the second evaluate its effect on oral pathogenic biofilms. Thus, formulations with different concentrations of chlorhexidine were prepared and evaluated visually for their physical integrity under the biofilm growth conditions, followed by the static media release assay using buffer as the dissolution medium (conventional dissolution medium). The selected formulation was subjected to static release tests containing the different bacterial culture broths as the dissolution medium. In the second stage of the work, the effect of the selected formulation was evaluated in cariogenic biofilms of Streptococcus mutans or periodontopathogenic biofilms of Porphyromonas gingivalis. Biofilms of S. mutans (n = 6) or P. gingivalis (n = 3) were formed in culture broths under glass slides for 6 and 3 days respectively, being exposed to one of the following treatments: 1) Formulation containing 92 % of chitosan and 8% of hydroxypropyl methylcellulose (CV, vehicle control) or 2) Formulation containing 82% of chitosan, 8% of hydroxypropyl methylcellulose and 10% of chlorhexidine (CHX, experimental group). A group without exposure to the formulation was included as negative control (CN). After the experimental period, bacterial viability, biofilms pH and quantification of chlorhexidine released into the culture broths were determined. Data were statistically analyzed by Tukey-Kramer and Tukey test with a level of significance of 5%. Results suggest that although chlorhexidine release from formulation in the culture broths of S. mutans and P. gingivalis was lower compared to the conventional dissolution medium (p <0.05), the treatment promoted biological effect for both biofilms. Regarding S. mutans biofilms pH, CN and CV groups showed no difference (p> 0.05), but showed higher pH drops when compared to CHX (p <0.05). CHX also resulted in lower bacterial viability of biofilms compared to controls (p <0.05), which did not show any difference (p> 0.05). For P. gingivalis, there was higher cell death in the biofilms exposed to CHX (p <0.05) and CV presented loss of viability compared to CN (p <0.05). Although the release of chlorhexidine from the formulation has been hampered by the presence of microorganisms, results suggest that the release system was able to reduce the pathogenicity of Streptococcus mutans and Porphyromonas gingivalis biofilms. Thus, the present study suggests the importance of combining studies from different areas of knowledge in order to contribute to the design of formulations aiming future clinical benefits for the oral diseases control.

A magnetic target drug delivery system consisting of biodegradable polymeric microspheres (poly D, L-lactic acid) loaded with magnetite nanoparticles (10-100 nm) and anticancer drug (paclitaxel) was studied. The magnetite nanoparticles were synthesized by chemical precipitation. The as-synthesized magnetite nanoparticles were subsequently introduced into a mixture of polymer magnetic polymeric composite particles were investigated and further correlated with the reaction parameters. It was found that the size and characteristics of the polymeric composite particles depended on the viscosity of the polymer solution. Preliminary drug release experiments showed that the loaded drug was released with the degradation of the polymer. The release rates could be enhanced by an oscillating external magnetic field. / Singapore-MIT Alliance (SMA)