Development and evaluation of alginate-based gastroretentive raft-forming systems enabling sustained release of propolis in gastric ulcer treatment

This study aimed to develop alginate-based raft-forming systems incorporating propolis-whey protein isolate (5%) nanocomplexes to alleviate reflux symptoms and enable the sustained, gastric-specific delivery of propolis for ulcer management. Propolis-protein complexes were prepared at four ratios (2.5:100, 5:100, 7.5:100, and 10:100 w/v) by heating at 85 °C for 5 h at pH 2, producing nanofibrils characterized by thioflavin T fluorescence, intrinsic fluorescence, encapsulation efficiency (up to 78%), and antioxidant activity. The optimal complex was incorporated into alginate rafts at 5%, 10%, and 15% (w/v). Rafts exhibited prolonged floatability (>8 h), increased thickness (from 3.2 ± 0.4 mm to 4.7 ± 0.3 mm with higher propolis loading), enhanced mechanical strength (up to 1.6-fold improvement), and improved reflux resistance. SEM imaging revealed a more compact and uniform porous structure, while FT-IR confirmed molecular interactions between alginate and the propolis-protein complex. <i>In vitro</i> release studies in simulated gastric fluid showed suppression of initial burst release, with sustained propolis release over 6-8 h. Overall, alginate rafts containing propolis-protein nanocomplexes demonstrated enhanced structural performance, controlled release behavior, and promising potential for targeted gastric delivery in the management of gastric ulcers.