Abstract
<title>Abstract</title> <p>Background Alendronate sodium, a widely prescribed bisphosphonate for osteoporosis, is associated with poor oral bioavailability and significant gastrointestinal side effects, leading to low patient compliance. Objective This study aimed to compare the gastrointestinal effects and pharmacokinetic profile of conventional oral alendronate sodium versus a novel nanoparticle-hydrogel formulation. Methods Alendronate nanoparticles were prepared using an ionotropic gelation technique with sodium alginate and calcium chloride as cross-linking agents. Wistar rats were divided into five groups. Gastric and esophageal tissues were examined histopathologically. Oxidative stress markers and antioxidant enzyme activities were measured in tissue homogenates. Results The nanoparticle-hydrogel formulation demonstrated improved pharmacokinetics with an 80.1% increase in Cmax and a 25.3% increase in AUC compared to uncoated alendronate, indicating substantially enhanced drug absorption and bioavailability. Histopathological analysis revealed significantly reduced tissue damage in both gastric and esophageal tissues for the nanoparticle-hydrogel group. Oxidative stress markers were significantly lower, while antioxidant enzyme activities were higher in the nanoparticle-hydrogel group compared to the uncoated drug group (p < 0.05), suggesting a protective mechanism that could translate into improved patient tolerance to treatment. Conclusion The nanoparticle-hydrogel formulation of alendronate demonstrates enhanced bioavailability and significantly reduced gastrointestinal side effects compared to conventional oral alendronate.</p>