BDTD - Biblioteca Digital de Teses e Dissertações
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Doctoral Thesis Desenvolvimento de sistemas terapêuticos para leishmaniose cutânea(2019-09-26) Alexandrino Júnior, Francisco; Egito, Eryvaldo Sócrates Tabosa do; ; ; Rocha, Helvecio Vinicius Antunes; ; Pohlmann, Adriana Raffin; ; Lima, Eliana Martins; ; Frezard, Frederic Jean Georges;This study aimed to develop therapeutic alternatives containing amphotericin B (AmB) for the treatment of cutaneous leishmaniasis. Therefore, polymeric systems with distinct geometry (films and fibers) and hydrophilicity (polyvinyl alcohol) and poly(lactic acid)) were produced, and their respective kinetic release profiles were evaluated and correlated with these production parameters and thermodynamic parameters. The data indicated that the drug release was an endothermic and non-spontaneous process, with the fibers and films appropriately fitting to Peppas – Sahlin and Higuchi’s model, respectively. Among the systems evaluated, PVA hydrogels performed the best controlled release and, therefore, their properties as a potential therapeutic system was further evaluated in vitro. The results highlighted that the system was able to control the water vapor permeation, at levels compatible with the skin in its physiological state, acted as a physical barrier against microorganisms present in the environment, and simultaneously displayed efficient antifungal and antileishmania activity, without potential cytotoxicity to renal cells (VERO cell line). Meanwhile, microemulsions (ME) containing 14 %w/w of poloxamer 407 were developed, which provided to the system a thermoreversible behavior (gelation in situ at ~ 25 °C), facilitating its topical application. The poloxamer 407 attenuated the instability phenomena in the ME system during the storage period at 2 °C, without affecting the half-life of the drug. Regarding the ex vivo dermal retention of AmB, it was possible to infer that ME acted as a permeabilizing agent, enabling after 24h of exposition, an AmB dermal retention of ~ 1,37 ± 0,75 g/cm2 . However, the presence of polymer in the system reduced the diffusion rate of AmB, in such a way that no drug was detected during the in vitro assay. Although there is a required in vivo endorsement, the results obtained here demonstrate that PVA hydrogels and thermo-responsive ME are promising systems for use in combination therapy, allowing for outpatient topical treatment of cutaneous leishmaniasis.Master Thesis Desenvolvimento de hidrogéis de poli (álcool vinílico) contendo anfotericina B para o tratamento de leishmaniose tegumentar americana(2015-03-31) Alexandrino Júnior, Francisco; Egito, Eryvaldo Sócrates Tabosa do; ; http://lattes.cnpq.br/6907806915889763; ; http://lattes.cnpq.br/7620675279773626; Balaban, Rosângela de Carvalho; ; http://lattes.cnpq.br/7711521318854102; Lione, Viviane de Oliveira Freitas; ; http://lattes.cnpq.br/7700565158061560