Work

3D-Printed Rebamipide Nanocrystal Oral Thin Films for Gastroprotection Against Indomethacin-Induced Gastric Lesions in Arthritic Rats

Year: 2026

Type: article

Abstract: Purpose: Gastric mucosal injury caused by long-term nonsteroidal anti-inflammatory drug therapy remains a significant clinical concern, particularly in patients with rheumatoid arthritis. In this study, we developed a three-dimensional (3D)-printed oral thin film (OTF) formulation incorporating rebamipide (REB) nanocrystals (REB-NP@OTF) with enhanced gastroprotective potential. Methods: REB nanocrystals were prepared by wet bead milling using methylcellulose and hydroxypropyl-β-cyclodextrin as stabilizers. The nanocrystals were incorporated into a polymeric OTF matrix using semi-solid extrusion-based 3D printing. Particle size was measured by nanoparticle tracking analysis using a NanoSight LM10 system, and in vitro drug release was compared with that from OTF containing micro-sized REB (REB@OTF). Gastric mucosal drug retention was evaluated using rats, and therapeutic efficacy was assessed in an indomethacin (IND)-induced gastric injury model using adjuvant-induced arthritis (AA) rats. Results: REB nanocrystals had a mean particle size of approximately 114 nm. Compared with REB@OTF, REB-NP@OTF exhibited a smoother and more uniform internal structure with densely packed particles. Both formulations satisfied the pharmacopeial criteria for weight and content uniformity; however, nanocrystal incorporation significantly altered the pharmaceutical properties. Compared to REB@OTF, REB-NP@OTF showed a 4.2-fold increase in solubility, enhanced hydration behavior, and faster drug release under simulated intestinal conditions. Importantly, particle size analysis confirmed that REB was released from REB-NP@OTF while maintaining its nanoparticulate state. In vivo studies revealed prolonged gastric mucosal retention following oral administration of REB-NP@OTF. In an IND-induced gastric acute injury model using AA rats, REB-NP@OTF markedly reduced the gastric lesion area relative to the REB@OTF containing conventional REB powder. Conclusion: These findings indicate that 3D-printed REB nanocrystal OTFs represent a promising and versatile strategy for improving gastroprotective therapy.

Source: International Journal of Nanomedicine

DOI: 10.2147/ijn.s654551