Thermosensitive poly (NVCL-co-GelMA) nanogels as a delivery platform for rectal administration of 5-ASA in ulcerative colitis

5-Aminosalicylic acid (5-ASA) is widely used in the clinical treatment of ulcerative colitis (UC), but its effectiveness is limited by poor patient compliance and inadequate drug retention. Herein, a novel thermoresponsive nanogel (P(NVCL-co-GelMA)) was synthesized through the copolymerization of N-vinylcaprolactam (NVCL) and methacrylated gelatin (GelMA). This nanogel serves as an effective carrier for 5-ASA, transitioning from a sol to a hydrogel at physiological temperatures, thereby enhancing drug retention and reducing leakage. In vitro studies revealed that the nanogel has a lower critical solution temperature of approximately 34 °C and can form a gel within 60 s. It demonstrates superior bioadhesion, biocompatibility, and controlled release of 5-ASA. In a rat model of UC, the 5-ASA-loaded nanogel significantly improved weight loss and disease activity index scores compared to untreated rats. The hydrogel coating acts as a biophysical barrier on the intestinal mucosa, effectively blocking the irritation caused by metabolites and maximizing the therapeutic effect, comparable to that of commercial mesalazine enema (Salofalk). The P(NVCL-co-GelMA) nanogel represents a promising drug delivery system for the treatment of UC, offering extended drug retention, reduced leakage, and enhanced therapeutic efficacy.