Cette thèse a été consacrée à la mise au point de deux systèmes d'administration destinés à la voie orale, pour deux molécules différentes.Dans la première partie, des microparticules (MPs) à base de xylane et d'Eudragit® S-100 ont été produites pour encapsuler l’acide 5-aminosalicylique et permettre son absorption au niveau du colon. Le xylane a été extrait à partir de rafles de maïs et caractérisé selon ses propriétés physico-chimiques, rhéologiques et toxicologiques. Par la suite, les MPs ont été préparées soit par réticulation interfaciale, soit par séchage par atomisation et caracterisés quant à leur morphologie, leur taille moyenne et leur distribution, leur stabilité thermique, leur cristallinité, leur efficacité et leur profil de libération du médicament in vitro. Des MPs de caractéristiques physiques appropriées avec des rendements satisfaisants ont été préparées par ces deux méthodes, bien que les systèmes séchés par pulvérisation aient montré une plus grande stabilité thermique. En général, ces derniers systèmes étaient plus prometteurs en raison de leur stabilité thermique et de l'absence d'agents réticulants toxiques. Toutefois, la méthodologie doit être optimiser afin d’améliorer le chargement de principe actif ainsi que sa libération.Dans la deuxième partie de cette thèse, des microémulsions huile-dans-l’eau (ME H/E) à base de triglycérides à chaîne moyenne ont été preparées afin de vectoriser et d’augmenter la solubilité de l'amphotéricine B (AmB). Des diagrammes de phases ont été construits en utilisant des mélanges de tensioactifs dont les valeurs de la balance hydrophile-lipophile variaient entre 9,7 et 14,4. Les MEs H/E sans et avec AmB étaient composées de gouttelettes sphériques non agrégées de diamètre moyen autour de 80 et 120 nm, respectivement, et avec une faible polydispersité. L'incorporation de l'AmB était élevée et dépendait de la fraction volumique de la phase dispersée. La viabilité des cellules J774.A1 n’était pas diminuée par l’exposition aux concentrations d’AmB encapsulée allant jusqu’à 25μg/mL. Par conséquent, les MEs H/E à base d’esters de propylèneglycol et d'acide caprylique peuvent être considéré comme des vecteurs adaptés pour l’AmB. / This thesis was devoted to the development of innovative oral delivery systems for two different molecules. In the first part, microparticles (MPs) based on xylan and Eudragit® S-100 were produced and used to encapsulate 5-aminosalicylic acid for colon delivery. Xylan was extracted from corn cobs and characterized in terms of its physicochemical, rheological and toxicological properties. The polymeric MPs were prepared by interfacial cross-linking polymerization and spray-drying and characterized for their morphology, mean size and distribution, thermal stability, crystallinity, entrapment efficiency and in vitro drug release. MPs with suitable physical characteristics and satisfactory yields were prepared by both methods, although the spray-dried systems showed higher thermal stability. In general, spray-dried MPs would be preferable systems due to their thermal stability and absence of toxic agents used in their preparation. However, drug loading and release need to be optimized. In the second part of this thesis, oil-in-water microemulsions (O/W MEs) based on medium-chain triglycerides were formulated as drug carriers and solubility enhancers for amphotericin B (AmB). Phase diagrams were constructed using surfactant blends with hydrophilic-lipophilic balance values between 9.7 and 14.4. The drug-free and drug-loaded MEs presented spherical non-aggregated droplets around 80 and 120 nm, respectively, and a low polydispersity index. The incorporation of AmB was high and depended on the volume fraction of the disperse phase. These MEs did not reduce the viability of J774.A1 macrophage-like cells for concentrations up to 25 µg/mL of AmB. Therefore, O/W MEs based on propylene glycol esters of caprylic acid may be considered as suitable delivery systems for AmB.

This thesis was devoted to the development of innovative oral delivery systems for two different molecules. In the first part, microparticles (MPs) based on xylan and Eudragit® S-100 were produced and used to encapsulate 5-aminosalicylic acid for colon delivery. Xylan was extracted from corn cobs and characterized in terms of its physicochemical, rheological and toxicological properties. The polymeric MPs were prepared by interfacial cross-linking polymerization and spray-drying and characterized for their morphology, mean size and distribution, thermal stability, crystallinity, entrapment efficiency and in vitro drug release. MPs with suitable physical characteristics and satisfactory yields were prepared by both methods, although the spray-dried systems showed higher thermal stability. In general, spray-dried MPs would be preferable systems due to their thermal stability and absence of toxic agents used in their preparation. However, drug loading and release need to be optimized. In the second part of this thesis, oil-in-water microemulsions (O/W MEs) based on medium-chain triglycerides were formulated as drug carriers and solubility enhancers for amphotericin B (AmB). Phase diagrams were constructed using surfactant blends with hydrophilic-lipophilic balance values between 9.7 and 14.4. The drug-free and drug-loaded MEs presented spherical non-aggregated droplets around 80 and 120 nm, respectively, and a low polydispersity index. The incorporation of AmB was high and depended on the volume fraction of the disperse phase. These MEs did not reduce the viability of J774.A1 macrophage-like cells for concentrations up to 25 µg/mL of AmB. Therefore, O/W MEs based on propylene glycol esters of caprylic acid may be considered as suitable delivery systems for AmB.

Submitted by Marlene Santos (marlene.bc.ufg@gmail.com) on 2016-09-21T19:09:33Z No. of bitstreams: 2 Dissertação - Francielle Campos Lima - 2016.pdf: 2372165 bytes, checksum: 338af5a42ce51711564e513a92bae046 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-09-26T11:33:09Z (GMT) No. of bitstreams: 2 Dissertação - Francielle Campos Lima - 2016.pdf: 2372165 bytes, checksum: 338af5a42ce51711564e513a92bae046 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2016-09-26T11:33:09Z (GMT). No. of bitstreams: 2 Dissertação - Francielle Campos Lima - 2016.pdf: 2372165 bytes, checksum: 338af5a42ce51711564e513a92bae046 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-02-25 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Schiff bases are imine compounds with wide applications in several are as of knowledge, highlighting mainly in the biology fields, especially for antimicrobials applications. The synthesis of six new Schiff bases (SB) are displayed. They were obtained from the direct condensation methanolic solutions of drugs already actives (4- and 5-ASA) with different aldehydes. The synthesized compounds were characterized as to their fusion point, solubility, CHN elementary analysis, infrared absorption spectroscopy, ultraviolet visible spectroscopy and nuclear magnetic resonance of hydrogen. The synthesized products were evaluated in bioassays on E. coli, S. aureus and P. aeruginosa strains. The nature of the characterized compounds class confirms the acquired products as objectified. Two biological results were obtained, as the analyzed variable, the composition of the prepared stock solution. With DMF, the results were biased, from which nothing can be stated because of the possibility of influencing as a false positive result. The other results using DMSO stock solution exhibited a positive prospect regarding the MIC values, with special attention to the BS6 and BS9 ligands wich showed better activity. / Bases de Schiff são compostos iminicos com amplas aplicações nas mais diversas áreas do conhecimento, destacando-se principalmente na área da biologia, com destaque para aplicações como antimicrobianos. A síntese de seis novas bases de Schiff (BS), obtidas a partir da condensação direta de soluções metanólicas de fármacos já ativos (4- e 5-ASA) com diferentes aldeídos, é apresentada. Os compostos sintetizados foram caracterizados quanto ao seu ponto de fusão, solubilidade, analise elementar CHN, espectroscopia de absorção na região do infravermelho, espectroscopia eletrônica na região do ultravioleta visível e espectroscopia de ressonância magnética nuclear de hidrogênio. Os produtos sintetizados foram avaliados em ensaios biológicos frente a estirpes de E. coli, S. aureus e P. aeruginosa. A natureza da classe de compostos caracterizada confirma a obtenção dos produtos conforme objetivado. Dois resultados dos ensaios biológicos foram obtidos, sendo a variável analisada, a composição da solução estoque preparada. Com DMF os resultados se apresentaram tendenciosos, a partir dos quais nada pode ser afirmado devido a possibilidade de influenciar em um resultado falso positivo. Já os demais resultados utilizando-se solução estoque com DMSO, exibiram um panorama positivo em relação aos valores de CMI, com atenção especial para os ligantes BS6 e BS9 que mostraram melhor atividade.

Made available in DSpace on 2014-12-17T14:13:48Z (GMT). No. of bitstreams: 1 AcariliaES_TESE.pdf: 9221805 bytes, checksum: 71876e327362584aeb9dcac7d3652c4d (MD5) Previous issue date: 2013-04-05 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / This thesis was devoted to the development of innovative oral delivery systems for two different molecules. In the first part, microparticles (MPs) based on xylan and Eudragit? S- 100 were produced and used to encapsulate 5-aminosalicylic acid for colon delivery. Xylan was extracted from corn cobs and characterized in terms of its physicochemical, rheological and toxicological properties. The polymeric MPs were prepared by interfacial cross-linking polymerization and spray-drying and characterized for their morphology, mean size and distribution, thermal stability, crystallinity, entrapment efficiency and in vitro drug release. MPs with suitable physical characteristics and satisfactory yields were prepared by both methods, although the spray-dried systems showed higher thermal stability. In general, spraydried MPs would be preferable systems due to their thermal stability and absence of toxic agents used in their preparation. However, drug loading and release need to be optimized. In the second part of this thesis, oil-in-water microemulsions (O/W MEs) based on mediumchain triglycerides were formulated as drug carriers and solubility enhancers for amphotericin B (AmB). Phase diagrams were constructed using surfactant blends with hydrophiliclipophilic balance values between 9.7 and 14.4. The drug-free and drug-loaded MEs presented spherical non-aggregated droplets around 80 and 120 nm, respectively, and a low polydispersity index. The incorporation of AmB was high and depended on the volume fraction of the disperse phase. These MEs did not reduce the viability of J774.A1 macrophage-like cells for concentrations up to 25 μg/mL of AmB. Therefore, O/W MEs based on propylene glycol esters of caprylic acid may be considered as suitable delivery systems for AmB / Esta tese teve como objetivo o desenvolvimento de novos sistemas de libera??o para duas mol?culas distintas. Na primeira parte, micropart?culas ? base de xilana e Eudragit? S-100 foram produzidas para encapsular ?cido 5-aminosalic?lico visando ? libera??o c?lonespec?fica. A xilana foi extra?da de sabugos de milho e caracterizada quanto ?s suas propriedades f?sico-qu?micas, reol?gicas e toxicol?gicas. Em seguida, dois m?todos de microencapsula??o foram utilizados: reticula??o interfacial polim?rica e secagem por aspers?o. Os sistemas produzidos foram caracterizados quanto ? morfologia, tamanho m?dio e distribui??o, estabilidade t?rmica, cristalinidade, taxa de encapsula??o e libera??o do f?rmaco in vitro. Foram obtidas micropart?culas com adequadas caracter?sticas f?sicas e rendimentos satisfat?rios atrav?s dos dois m?todos, embora os sistemas aspergidos tenham apresentado maior estabilidade t?rmica e sejam considerados mais interessantes devido a sua maior estabilidade t?rmica e aus?ncia de agentes t?xicos. No entanto, ajustes precisam ser feitos para melhorar a encapsula??o e libera??o do f?rmaco. Na segunda parte, microemuls?es do tipo ?leo em ?gua (MEs O/A) com base em triglicer?deos de cadeia m?dia (MCT) foram produzidas visando ao carreamento de anfotericina B (AmB) e aumento da sua solubilidade. Foram obtidas MEs O/A sem e com AmB com got?culas em torno de 80 e 120 nm, respectivamente, e ?ndices de polidispers?o de 0,25 e 0,31, respectivamente. A taxa de incorpora??o da AmB foi alta e dependente do volume da fase dispersa. A viabilidade celular n?o foi afetada at? 25 μg/mL da AmB. Portanto, MEs O/A a partir de MCT podem ser promissores sistemas de libera??o para AmB