5-aminosalicylic acid pH sensitive core-shell nanoparticles targeting ulcerative colitis

In this study, a pH sensitive 5-aminosalicylic acid core-shell nanoparticles (ES1CS5SA5@5-ASANCs) were prepared used for colon targeted therapy of ulcerative colitis (UC). 5-Aminosalicylic acid nanocrystals (5-ASANCs) were prepared by anti-solvent crystallization technology, and then CS5SA5@5-ASANCs were prepared by coating chitosan (CS) and sodium alginate (SA) directly on the nanocrystals by layer-by-layer (LBL) self-assembly technology. Finally, CS5SA5@5-ASANCs were coated with Eudragit®S100 (ES) to successfully prepared ES1CS5SA5@5-ASANCs. The particle size, zeta potential, entrapment efficiency (EE) and drug loading (DL) were 352 ± 2 nm, + 36 ± 1 mV, 95.05 ± 3.83% and 85.73 ± 2.12%, respectively. The distinct core-shell structure of nanoparticles can be observed by transmission electron microscopy (TEM). In vitro release studies showed that the core-shell structure enhanced the stability of 5-ASANCs, prevented the early release of drugs, and made 5-ASA release less in the upper gastrointestinal tract (GIT) pH environment, but sustained in the colon. The study of biological distribution in vivo showed that ES1CS5SA5@5-ASANCs selectively accumulate in the colon. Addition, the mucus-penetrating experiment revealed that the multilayer polymer structure can significantly enhance the mucus penetration capacity of the nanoparticles. Importantly, ES1CS5SA5@5-ASANCs showed significant therapeutic effect on ulcerative colitis mice. Overall, ES1CS5SA5@5-ASANCs could be a perspective drug delivery system for the treatment of ulcerative colitis.