Abstract

Owing to the low solubility of 5-aminosalicylic acid (5-ASA), a first-line drug for treatment of ulcerative colitis (UC), oral and local administration are challenging, leading to a low utilization rate. Here, we applied generation 4 polyamidoamine (G4 PAMAM) dendrimer to construct a G4-ASA nanoparticle, via a host–guest interaction, containing surface amino groups to crosslink the aldehyde group of the oxidized dextran by a Schiff base reaction, yielding an injectable adhesive 5-ASA-loaded hydrogel (G4-ASA/Dex). This slow-release 5-ASA agent was then injected rectally to dextran sulfate sodium (DSS)-induced UC mice. 5-ASA solubility increased 25.62-fold (from 0.903 mg/mL to 23.131 mg/mL) in G4-ASA nanoparticles, while the hydrogel exhibited structural stability, mucoadhesivity, and acid-responsive drug release. Thus, the G4-ASA/Dex was injectable, convenient for rectal delivery, and exhibited an outstanding adhesive effect. Furthermore, G4-ASA/Dex more effectively maintained colon length and reduced intestinal inflammatory cell infiltration compared with traditional administration, while exhibiting optimal performance in terms of the disease activity index, histological scoring, and immunohistochemical results. Hence, this new model could improve the solubility and utilization of 5-ASA for clinical use, thereby, serving as an effective local treatment strategy for intestinal inflammation.