Avaliação de uma pectina de alto grau de esterificação na retrogradação do amido e Desenvolvimento de filmes para liberação cólon-específica
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Data
2021-12-13
Autores
Ferraz, Jessica
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Universidade Estadual Paulista (Unesp)
Resumo
Doença Inflamatória intestinal (DII) caracteriza-se como uma inflamação crônica do trato gastrointestinal, e possui como terapia fundamental o fármaco ácido 5-aminosalicílico (5-ASA), o qual apresenta ação sistêmica e é desprovido de seletividade. Uma maneira de contornar essa limitação e otimizar o efeito terapêutico é proporcionando uma terapia localizada, o que pode ser alcançado através da elaboração de sistemas de liberação cólon-específicos baseados em amido retrogradado (AR). A avaliação do impacto da pectina de alto grau de esterificação é fundamental para otimização deste excipiente colônico e posterior obtenção de filmes poliméricos. Sendo assim, o objetivo desse trabalho foi avaliar e caracterizar o impacto de uma pectina de alto grau de esterificação na retrogradação do amido para posterior produção de filmes poliméricos destinados à liberação colônica do 5-ASA. O amido foi retrogradado através de tratamento hidrotérmico com ciclos alternados de temperatura. Posteriormente, o teor do AR foi analisado por digestão enzimática e determinação de glicose pelo método de açúcar redutor. Produziu-se filmes utilizando dispersões filmógenas retrogradadas, através do método de evaporação do solvente e esses foram avaliados morfologicamente por MEV-FEG realizado em microscópio JEOL JSM-7500F (Japão). As propriedades mecânicas foram determinadas em analisador universal de textura TA-XT2 Texture Analyser, assim como o ensaio de mucoadesão utilizando discos de mucina. A absorção de líquidos e o perfil de liberação in vitro foram avaliados utilizando meios com pH que mimetizam as diferentes porções do TGI. A retrogradação do amido ocorreu adequadamente e os valores de AR variaram entre 39,57% e 58,14%. Os filmes obtidos apresentaram integridade, flexibilidade, alongamento, resistência mecânica e rugosidade. Além disso, os filmes exibiram elevada afinidade pela mucina, demonstrado altas forças de destacamento. A absorção de líquidos foi maior em pH 6,8 em filmes de AR/P50 (18396%), e a liberação in vitro ocorreu de maneira não dependente do pH, alcançado de 80% a 90% de liberação logo nos primeiros 60 min em meio ácido. Conclusão: As propriedades morfológicas, estruturais, mecânicas e de mucoadesão sugerem que os novos filmes são excelentes candidatos como filme de revestimento de forma farmacêuticas sólidas. Contudo, a não seletividade da liberação em meio colônico exige uma maior investigação para entendimento das relações estrutura-atividade, principalmente quando da incorporação do fármaco 5-ASA.
Inflammatory Bowel Disease (IBD) is characterized as a chronic inflammation of the gastrointestinal tract, and its fundamental therapy is the drug 5-aminosalicylic acid (5-ASA), which has systemic action and lacks selectivity. One way to get around this limitation and optimize the therapeutic effect is to provide a localized therapy, which can be achieved through the development of colon-specific delivery systems based on retrograded starch (RA). The evaluation of the impact of pectin with a high degree of esterification is essential for optimizing this colonic excipient and later obtaining polymeric films. Therefore, the objective of this work was to evaluate and characterize the impact of a pectin with a high degree of esterification on starch retrogradation for subsequent production of polymeric films for the colonic release of 5-ASA. Starch was retrograded by hydrothermal treatment with alternating temperature cycles. Subsequently, the AR content was analyzed by enzymatic digestion and glucose determination by the reducing sugar method. Films were produced using retrograde film-forming dispersions, through the solvent evaporation method and these were morphologically evaluated by MEV-FEG performed in a JEOL JSM-7500F microscope (Japan). Mechanical properties were determined in a universal texture analyzer TA-XT2 Texture Analyzer, as well as the mucoadhesion test using mucin discs. The liquid absorption and the in vitro release profile were evaluated using media with pH that mimic the different portions of the TGI. Starch retrogradation occurred properly and AR values ranged between 39.57% and 58.14%. The films obtained showed integrity, flexibility, elongation, mechanical strength and roughness. Furthermore, the films exhibited high affinity for mucin, demonstrating high detachment strengths. Liquid absorption was higher at pH 6.8 in AR/P50 films (18396%), and in vitro release occurred in a non-pH dependent manner, reaching 80% to 90% release in the first 60 min in acidic medium. Conclusion: The morphological, structural, mechanical and mucoadhesion properties suggest that the new films are excellent candidates as coating films for solid dosage forms. However, the non-selectivity of release in colonic medium requires further investigation to understand the structure-activity relationships, especially when incorporating the drug 5-ASA.
Inflammatory Bowel Disease (IBD) is characterized as a chronic inflammation of the gastrointestinal tract, and its fundamental therapy is the drug 5-aminosalicylic acid (5-ASA), which has systemic action and lacks selectivity. One way to get around this limitation and optimize the therapeutic effect is to provide a localized therapy, which can be achieved through the development of colon-specific delivery systems based on retrograded starch (RA). The evaluation of the impact of pectin with a high degree of esterification is essential for optimizing this colonic excipient and later obtaining polymeric films. Therefore, the objective of this work was to evaluate and characterize the impact of a pectin with a high degree of esterification on starch retrogradation for subsequent production of polymeric films for the colonic release of 5-ASA. Starch was retrograded by hydrothermal treatment with alternating temperature cycles. Subsequently, the AR content was analyzed by enzymatic digestion and glucose determination by the reducing sugar method. Films were produced using retrograde film-forming dispersions, through the solvent evaporation method and these were morphologically evaluated by MEV-FEG performed in a JEOL JSM-7500F microscope (Japan). Mechanical properties were determined in a universal texture analyzer TA-XT2 Texture Analyzer, as well as the mucoadhesion test using mucin discs. The liquid absorption and the in vitro release profile were evaluated using media with pH that mimic the different portions of the TGI. Starch retrogradation occurred properly and AR values ranged between 39.57% and 58.14%. The films obtained showed integrity, flexibility, elongation, mechanical strength and roughness. Furthermore, the films exhibited high affinity for mucin, demonstrating high detachment strengths. Liquid absorption was higher at pH 6.8 in AR/P50 films (18396%), and in vitro release occurred in a non-pH dependent manner, reaching 80% to 90% release in the first 60 min in acidic medium. Conclusion: The morphological, structural, mechanical and mucoadhesion properties suggest that the new films are excellent candidates as coating films for solid dosage forms. However, the non-selectivity of release in colonic medium requires further investigation to understand the structure-activity relationships, especially when incorporating the drug 5-ASA.
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Palavras-chave
liberação cólon-específica, amido retrogradado, pectina, doença inflamatória intestinal, 5-ASA, filmes poliméricos, colon-specific release, retrograded starch, pectin, inflammatory bowel disease, polymeric films