Controlled drug delivery systems are becoming increasingly interesting with the contribution of nanotechnology. In the case of transdermal applications the greatest limitation is the highly impermeable outermost layer of the skin, the stratum corneum. One promising method of controlled transdermal drug delivery of the skin therapeutics is the use of nanoparticles as carriers. Encapsulation of the drug, as opposed to classical topical application of creams or emulsions, allows the drug to diffuse into hair follicles where drug release can occur in the deeper layers of the skin. The aim of this study was to develop micro and nano sized carriers as drug delivery systems to achieve treatment for skin conditions like psoriasis, aging or UV damage, caused by radiation or health problems. Two different types of bioactive agents, retinyl palmitate (RP) and Dead Sea Water (DSW), were used by encapsulating in poly(3-hydroxybutyrate-co-3-hydroxyvalerate) carriers. In some tests MgCl2 was used as a substitute for DSW when quantification was needed. Bioactive agent loaded nanospheres and nanocapsules were prepared with o/w and w/o/w methods in low micron (1.9 &micro / m), mid nano (426 nm) and nano (166 nm) sizes. Loading, encapsulation efficiency and release kinetics were studied. The encapsulation efficiency and loading values are low especially for the water soluble agents, DSW and MgCl2. It was observed that the capsules loaded with hydrophilic agents released their content in the first 24 h in aqueous media. The encapsulation efficiency and loading values for RP were higher because of the insolubility of the agent in water. In the in vitro studies carried out with L929 mouse fibroblast cells, the nano sized PHBV capsules were detected in the cytoplasm of the cells. Cell viability assay (MTT) for L929 cells showed a growth trend indicating that the particles were not cytotoxic and the values were close to the controls. Hemolytic activity was examined using human erythrocytes and micro/nanoparticles of PHBV were found to be non hemolytic. In vivo testing with BALB/c mice, nanocapsule penetration revealed that a small amount of nano sized particles penetrated the mice skin, despite the highly impermeable outer skin layer. As a result, PHBV micro/nanoparticles have a significant potential for use as topical drug delivery systems in the treatment of skin diseases.

Orientador: Francisco Benedito Teixeira Pessine / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-24T11:11:00Z (GMT). No. of bitstreams: 1 Barboza_AnaClaudiaRuedaNery_D.pdf: 6657696 bytes, checksum: 97ec0acb030267fe87c6983093726afb (MD5) Previous issue date: 2013 / Resumo: O objetivo foi deste trabalho foi obter, caracterizar e avaliar suspensões aquosas de micropartículas poliméricas bioadesivas para liberação sustentada do antisséptico digluconato de clorexidina (CHG), trabalhando somente em meio aquoso e com substâncias reconhecidamente biocompatíveis e de baixa toxicidade, para potencial aplicação na cavidade bucal. As micropartículas foram obtidas por complexação dos polieletrólitos quitosana e alginato de sódio, com auxílio de íons cálcio, e da clorexidina. O método de obtenção desenvolvido permitiu obter suspensões com distribuição de diâmetros de partículas adequada e boa estabilidade. Através de delineamento experimental fatorial, avaliou-se o efeito dos principais componentes da suspensão sobre o diâmetro médio das micropartículas e sobre a incorporação de CHG. A liberação de CHG em meio simulador da cavidade oral (saliva artificial) ocorreu de forma gradual e por longos períodos, indicando existência de interação entre o ativo, de natureza catiônica, e as terminações aniônicas do biopolímero alginato. A cinética de liberação de sistemas onde tais interações ocorrem é complexa e sua compreensão envolve diversos fenômenos físico-químicos, que se procurou identificar e discutir. Realizou-se, de forma simplificada, a modelagem da cinética de liberação através do modelo matemático semiempírico de Peppas-Korsmeyer, o que também indicou a combinação de diferentes fenômenos influenciadores da liberação. Testes preliminares de eficácia antimicrobiana indicaram que a clorexidina do sistema de liberação sustentada manteve sua eficácia sobre os microrganismos padrão avaliados em comparação com a clorexidina livre / Abstract: The objective of this project was to obtain, characterize and evaluate aqueous suspensions of bioadhesive polymeric microparticles for sustained release of the antiseptic chlorhexidine digluconate (CHG), working in aqueous media and with substances recognized as biocompatible and of low toxicity, for potential application to the oral cavity. Microparticles were obtained by complexation of the polyelectrolytes chitosan and sodium alginate, with pre-gelation by calcium ions, and CHG. The method of obtention developed resulted in suspensions with adequate particle size distribution and good stability. Through factorial experimental design, the effect of main suspension components on the median particle diameter and CHG incorporation was evaluated. Chlorhexidine release in oral cavity simulating media (artificial saliva) occurred gradually and for extended periods, indicating the presence of interactions between the cationic active substance, and the anionic moieties of the alginate biopolymer. The release kinetics where those interactions occur is somewhat complex and its understanding involves various physicochemical phenomena that we tried to identify and discuss. Simplified modeling of the release kinetics through the Peppas-Korsmeyer semi-empirical mathematical model was done, also indicating the combination of various release-influencing phenomena. Preliminary microbiological tests indicated that sustained-release CHG kept its efficacy against standard microorganisms evaluated in comparison to free CHG / Doutorado / Físico-Química / Doutora em Ciências