Albumin-Based Cryogels as Floating Platforms for Gastroretentive Drug Delivery Applications

Gastroretentive drug delivery systems (GRDDS) are attractive oral extended-release dosage forms that prolong drug release and absorption in the gastrointestinal tract through engineered mechanisms to extend the residence time of orally administered dosage forms in the stomach. One of the gastroretentive designs is to render the dosage forms floatable in the gastric fluid upon oral administration. The present study aimed to develop albumin cryogels with extended buoyancy and remarkable resistance to gastric proteolysis. Protein hydrogel monoliths can be prepared through thiol-organosilane-mediated hydrogelation of bovine serum albumin, followed by lyophilization to remove water, thereby producing cryogels. The study demonstrates that, by adjusting the composition of Na₂HPO₄ and sodium alginate in the hydrogel formulation, protein degradability can be effectively tuned to produce an intact floating structure with sustained buoyancy for over 24 h in simulated gastric fluid. This result is consistent with the finding that fluorescein, as a model payload, generally exhibited a decreased release rate from the formulations with increasing concentrations of Na₂HPO₄ and alginate. Notably, above a threshold concentration (i.e., about 2%) of alginate, the hydrogel monolith rapidly disintegrated in nearly neutral environments such as water and simulated intestinal fluid, exhibiting pH-responsive characteristics. Finally, the generalizability of the albumin-organosilane-alginate system as a promising controlled-release platform is further demonstrated in expanded application examples, using doxorubicin, mitoxantrone, methylene blue, and rhodamine 6G as the loaded payload; all exhibiting reproducible controlled-release profiles for the alginate-doped formulation. This finding can be explained by the SEM images showing smaller and denser porous structures with thicker, fiber-tangled intercompartment walls for gels with high alginate concentrations. Overall, the freeze-dried albumin-organosilane-alginate cryogel formulation demonstrates excellent buoyancy, resistance to degradation by simulated gastric fluid, and the ability to regulate drug release, highlighting its feasibility as a GRDDS.