Dual-action microparticles for ulcerative colitis: Cellulose nanofibers-enhanced delivery of 5-ASA and probiotics

Abstract

Ulcerative colitis (UC) is a chronic inflammatory bowel disease initially treated with mesalazine (5-ASA). However, its effectiveness is limited by rapid absorption, low colonic concentration, and exacerbation of dysbiosis. Probiotics can mitigate dysbiosis if they survive the acidic conditions of the stomach. In this study, colon-specific microparticles (MPs) based on RS/P and reinforced with cellulose nanofibers (CNF) were used to co-encapsulate 5-ASA and L. rhamnosus. MPs prepared by spray-drying demonstrated a spherical shape, with sizes ranging from 1 to 10 μm, high encapsulation efficiency (up to 81.5 %), and maintenance of L. rhamnosus viability (5.74 log CFU/g of sample) even after 30 days of storage at 4 °C. Differential scanning calorimetry indicated a reduction in the melting peak of 5-ASA after microencapsulation, suggesting a decrease in its crystallinity. The samples also exhibited high mucoadhesivity, with the presence of CNF significantly increasing the speed of establishing interactions with mucin. In vitro release profiles showed lower release rates in acidic media, resulting in the majority of 5-ASA being released in intestinal and colonic media. These MPs represent a promising strategy for promoting specific release in the colon, minimizing side effects associated with conventional treatment, and potentially improving therapeutic efficacy in the context of UC.