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Bioresponsive systems based on retrograded starch/pectin containing cellulose nanofibers as a strategy for 5-ASA colonic delivery in the treatment of Inflammatory Bowel Disease

Grant number: 19/19817-3
Support Opportunities:Scholarships in Brazil - Post-Doctorate
Effective date (Start): January 01, 2020
Effective date (End): August 25, 2022
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Principal Investigator:Marlus Chorilli
Grantee:Andréia Bagliotti Meneguin
Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil


Inflammatory Bowel Diseases (IBD) are considered a set of autoimmune disorders characterized by chronic inflammation, mucosal ulcerations and gastrointestinal hemorrhage. 5-Aminosalicylic acid (5-ASA) is the drug of choice in the treatment of mild to moderate IBD. For this drug to exert a pronounced therapeutic effect it is necessary to avoid its release in the upper portions of the Gastrointestinal Tract (GIT) and promote its release in the colonic region, which contributes to a localized treatment with significant reduction of side effects. Several strategies have been considered to vectorize 5-ASA for the colon, such as the use of prodrugs, the development of pH and/or time-dependent systems, as well as those activated by the colonic microbiota. Among the reported approaches, the development of systems employing enzymatic biodegradable polysaccharides has been considered the most reliable way to release drugs into the colon. In this scenario, Retrograded Starch (RS), a modified starch obtained by hydrothermal treatment (retrogradation), has been considered a promising candidate for the building of colonic systems. This is because this fraction of starch escapes digestion in the upper portions of the GIT and is digested only when it reaches the colon. Its association with pectin (P) was attributed to the optimization of the retrogradation process, increasing the AR yield, and leading to obtaining dispersions with excellent coating capacity of solid dosage forms for colonic release. However, the high aqueous solubility of P remains an important challenge regarding the increased resistance of this material to the different portions of GIT. The use of high esterification Ps (lower aqueous solubility) as well as the addition of cellulose nanofibers (NFC) as reinforcement can be considered promising strategies in the optimization of the AR/P excipient. Given the above, this research project aims to develop bioresponsive systems from the optimized excipient AR/P/NFC for targeting 5-ASA to the colon in the treatment of IBD. The characterization of materials and validation of the methodologies will be performed as well as in vitro and also in vivo assays, in order to prove the effectiveness of the proposed new systems. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MENEGUIN, ANDREIA BAGLIOTTI; SABIO, RAFAEL MIGUEL; DE SOUZA, MAURICIO PALMEIRA CHAVES; FERNANDES, RICHARD PEROSA; DE OLIVEIRA, ANSELMO GOMES; CHORILLI, MARLUS. Cellulose Nanofibers Improve the Performance of Retrograded Starch/Pectin Microparticles for Colon-Specific Delivery of 5-ASA. PHARMACEUTICS, v. 13, n. 9, . (19/19817-3, 14/50928-2)
MENEGUIN, ANDREIA BAGLIOTTI; SILVESTRE, AMANDA LETICIA POLLI; SPOSITO, LARISSA; DE SOUZA, MAURICIO PALMEIRA CHAVES; SABIO, RAFAEL MIGUEL; ARAUJO, VICTOR HUGO SOUSA; CURY, BEATRIZ STRINGHETTI FERREIRA; CHORILLI, MARLUS. The role of polysaccharides from natural resources to design oral insulin micro- and nanoparticles intended for the treatment of Diabetes mellitus: A review. Carbohydrate Polymers, v. 256, . (19/09597-6, 14/50928-2, 19/19817-3)
MENEGUIN, ANDREIA; PACHECO, GUILHERME; SILVA, JHONATAN MIGUEL; DE ARAUJO, FRANCISCA PEREIRA; SILVA-FILHO, EDSON CAVALCANTI; BERTOLINO, LUIZ CARLOS; BARUD, HERNANE DA SILVA. Nanocellulose/palygorskite biocomposite membranes for controlled release of metronidazole. International Journal of Biological Macromolecules, v. 188, p. 689-695, . (13/07793-6, 19/19817-3, 18/25512-8)

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