Innovation in the treatment of Inflammatory Bowel Disease: triple therapy with multifunctional nano-in-micro systems of 5-ASA, probiotics and sodium butyrate nanoparticles

• Grant number: 24/09833-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: December 01, 2024
• End date: March 31, 2028
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Andréia Bagliotti Meneguin
• Grantee: Vinicius Martinho Borges Cardoso
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Inflammatory bowel disease (IBD) causes persistent inflammation in the gastrointestinal tract (GI), leading to various complications. Among these, dysbiosis stands out, which is associated with exacerbating IBD symptoms, negatively impacting treatment response. Moreover, the chronic inflammation characteristic of IBD compromises GI mucosal integrity, reducing mucin production and rendering the intestinal mucosa more vulnerable to damage, thereby worsening the condition and hindering recovery. 5-Aminosalicylic acid (5-ASA) is used in IBD treatment; however, its effectiveness is limited due to predominant absorption in the upper GI tract, leading to the formation of the inactive metabolite N-acetyl-5-ASA and associated adverse effects, including exacerbation of pre-existing dysbiosis. Oral administration of probiotics (PROB) may mitigate dysbiosis in IBD, provided these microorganisms can withstand acidic conditions and upper GI enzymes. Alongside PROBs, sodium butyrate (BUT), a short-chain fatty acid, exhibits notable anti-inflammatory properties and potential interaction with the MUC2 gene responsible for mucin synthesis, promoting restoration of GI mucosal integrity. To increase BUT concentration in the colon, its incorporation into colon-specific carrier systems based on bioreponsive and colon-selective polymer nanoparticles (NPs), such as chitosan (QS), represents an effective strategy. NPs enhance interaction with the biological system, determining depth of penetration into intestinal mucosa, thus facilitating targeted drug delivery to inflamed regions in IBD. However, due to QS gastric solubility, incorporation of QS-NPs containing BUT into retrograded starch/pectin-based microparticles (nano-in-microparticles) is necessary. Starch retrogrades resist digestion in the stomach and small intestine, while pectin forms a gel in acidic pH, making it an ideal candidate for drug release in the colon. Therefore, this research project aims to co-encapsulate 5-ASA, NP-BUT, and probiotics in AR/P microparticles via spray drying, to develop stable and effective nano-in-microparticle systems for these bioactive compounds. It is anticipated that nano-in-microparticles will protect probiotics from gastric acidity, enhance survival during GI transit, and provide controlled release of 5-ASA and NP-BUT in the colon to optimize therapeutic efficacy. (AU)