Development and characterization of mucus-adhesive colon-specific nanoparticles based on chitosan/TPP and coated with gelatin gum for the treatment of inflammatory bowel disease

• Grant number: 24/22650-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2025
• End date: March 31, 2026
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Andréia Bagliotti Meneguin
• Grantee: Túlio Drago
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation of the gastrointestinal tract, resulting in symptoms such as abdominal pain and diarrhea. Its etiology is complex, involving genetic, environmental, and immunological factors. Thus, initial pharmacotherapy often includes aminosalicylates, such as 5-aminosalicylic acid (5-ASA), which is widely recognized as the "gold standard" in the treatment of IBDs. It acts effectively in inducing and maintaining disease remission due to its direct anti-inflammatory action on the intestinal mucosa, which reduces inflammation and promotes the healing of lesions. However, several pharmacokinetic challenges, such as high pre-systemic metabolism, result in low oral bioavailability, and its reduced ability to reach the colon in effective concentrations-where it is most needed for the treatment of IBD-must be addressed to ensure that pharmacotherapy is not compromised. To overcome these issues, the use of natural and colon-selective polysaccharides, such as chitosan (CS) and gelatin gum (GG), has shown promise for the development of colon-specific delivery systems. The use of CS is a promising strategy to enhance drug accumulation directly at the site of action, avoiding first-pass metabolism. The mucoadhesion of CS is crucial, as it ensures that the nanoparticles (NPs) remain in the colonic region, even in patients with accelerated intestinal transit. However, a significant challenge for its use is its solubility in acidic media, such as that found in the stomach. This property can result in the dissolution of CS before it reaches the colon, thus limiting its effectiveness as a carrier for colon-specific drug release. An important technological tool to overcome this limitation is the coating of CS NPs with GG, which has colon-specific behavior and pH-dependent solubility, making it resistant to the acidic conditions of the stomach, and also possesses well-established mucoadhesive properties. Given this context, CS NPs coated with GG aim to protect the drug from degradation in gastric pH and from first-pass metabolism, ensuring its controlled release in the colon while promoting a better quality of life and greater treatment adherence among patients with IBD.