Design and Characterization of Bovine Serum Albumin Hydrogels: A Promising Platform for Controlled Drug Delivery.

Protein-based hydrogels have attracted increasing interest as biocompatible matrices for drug delivery; however, simple systems based exclusively on albumin remain relatively underexplored. Here, we report the formation of bovine serum albumin (BSA) hydrogels generated through mild thermal aggregation (65 °C) without chemical cross-linkers, employing low protein concentrations (1-1.5%). The influence of the buffering environment (PBS vs Tris-HCl) on hydrogel architecture was identified as a key structural determinant. The resulting hydrogels were systematically characterized in terms of their structure, swelling behavior, water content, biodegradability, and morphology. Microscopic analyses revealed that Tris-HCl promoted the formation of a homogeneous and dense amyloid-like fibrillar network, whereas PBS led to more heterogeneous and irregular architectures. These structural differences affected the capacity to absorb and release model compounds with distinct physicochemical properties, producing sustained and matrix-dependent release profiles. In vitro assays demonstrated progressive degradation under physiological conditions, while in vivo murine models showed minimal immunological response.