Co-encapsulation of 5-aminosalicylic acid drug and probiotics in colon-specific retrograded starch/pectin microparticles, optimized with cellulose nanofibers, for the treatment of ulcerative colitis

• Grant number: 23/04633-0
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2024
• End date: January 31, 2026
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Andréia Bagliotti Meneguin
• Grantee: Andréia Bagliotti Meneguin
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated researchers: BEYSSAC ; Fernando Rogério Pavan ; Ghislain Garrait ; Marlus Chorilli

Abstract

Inflammatory bowel disease (IBD) is a chronic disorder affecting the gastrointestinal tract (GIT), with symptoms that include abdominal pain, diarrhea, and rectal bleeding. It includes two main types: ulcerative colitis and Crohn's disease. The main goal of IBD treatment is to reduce inflammation, control symptoms, and prevent complications, being performed with anti-inflammatories, immunomodulators, and biologic therapies such as anti-TNF agents. One of the main treatments for IBD is 5-aminosalicylic acid (5-ASA), especially for mild to moderate cases. However, its effectiveness is limited by its inability to reach the main site of inflammation in the colon at optimal concentrations. This is because 5-ASA is extensively absorbed in the upper portions of the GIT, which is metabolized into the inactive metabolite N-acetyl-5-ASA, in addition to being related to a series of adverse effects that reduce adherence to treatment. Disbiosis is another issue associated with 5-ASA use. The selectivity of 5-ASA and probiotics for the colon can be achieved through their co-encapsulation in colon-specific microparticles of retrograded starch (RS) and pectin (P) by spray-drying process. That's because RS is a modified starch with insoluble amylose and amylopectin complexes, which are highly resistant to digestion by enzymes in the small intestine. In addition, P forms a gel when exposed to low pH (such as gastric pH), making it an ideal candidate for targeted drug delivery in the colon. Recently, we used cellulose nanofibers (CNF) as a nano-reinforcement of the RS/P blend and optimized properties were found regarding the protection of premature drug release in undesirable portions of the GIT. For the co-encapsulation of 5-ASA and probiotics using the mentioned polymers, spray drying deserves attention as it offers several advantages for microencapsulation. Spray drying is a fast, continuous, one-step and cost-effective method widely used pharmaceutical industry, which can be easily scaled up, enabling large-scale production of microencapsulated products. Given the above, this research project aims the co-encapsulation of 5-ASA and probiotics in microparticles of RS/P/CNF by spray drying to develop a stable and effective delivery system for these bioactive compounds that can provide targeted delivery to the colon. The encapsulated formulation should be able to protect the probiotics from gastric acidity and enhance their survival during GIT transit, while also providing controlled release of 5-ASA in the colon to improve its therapeutic efficacy. The use of RS/P/CNF as encapsulating agents and spray drying as the encapsulation method is expected to result in a formulation with desirable physicochemical properties, such as high encapsulation efficiency, uniform particle size distribution, and good stability during storage. (AU)

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)

LOPES, SILVIO ANDRE; CARDOSO, VINICIUS MARTINHO BORGES; ROQUE-BORDA, CESAR AUGUSTO; CHORILLI, MARLUS; MENEGUIN, ANDREIA BAGLIOTTI. Dual-action microparticles for ulcerative colitis: Cellulose nanofibers-enhanced delivery of 5-ASA and probiotics. International Journal of Biological Macromolecules, v. 291, p. 13-pg., 2024-12-27. (23/04633-0)

SALES, LUCIANA SOLERA; DE FARIAS, ALINE LEITE; MENEGUIN, ANDREIA BAGLIOTTI; BARUD, HERNANE DA SILVA; BRIGHENTI, FERNANDA LOURENCAO. Carvacrol incorporation into novel controlled-release mucoadhesive systems for oral polymicrobial biofilm control. BIOFOULING, v. N/A, p. 11-pg., 2024-11-06. (19/26066-4, 19/08375-0, 23/04633-0, 21/12931-5)

MENEGUIN, ANDREIA BAGLIOTTI; ROQUE-BORDA, CESAR AUGUSTO; PIPERAS, ANA BEATRIZ GROTTO; POLLINI, MARIA FERNANDA ORTOLANI; CARDOSO, VINICIUS MARTINHO BORGES; PRIMO, LAURA MARIA DURAN GLERIANI; ALEMI, FOROGH; PAVAN, FERNANDO ROGERIO; CHORILLI, MARLUS. Nanofiber-boosted retrograded starch/pectin microparticles for targeted 5-Aminosalicylic acid delivery in inflammatory bowel disease: In vitro and in vivo non-toxicity evaluation. Carbohydrate Polymers, v. 346, p. 10-pg., 2024-08-28. (23/04633-0, 23/01664-1, 23/15205-9, 20/16573-3, 23/10440-0, 22/16773-8, 19/19817-3)