Protein Nanospheres and Nanofibers Prepared by Ice-Templating for the Controlled Release of Hydrophobic Drugs

Protein scaffolds play a vital role in drug delivery systems. However, few research studies have been focused on loading hydrophobic drugs on protein scaffolds in biomedical fields. Here, we report on the development of protein microspheres and nanofibers by a simple ice-templating approach and their use as scaffolds for the controlled release of hydrophobic drugs, with bovine serum albumin (BSA) as the model protein and curcumin as the model hydrophobic drug. The BSA scaffolds display the unique nanofibrous and microspherical structures. This is a surprising discovery because there has been no report on the formation of microspheres via simple ice-templating of solutions or suspensions. To further understand the formation of microspheres by this approach, lysozyme, papain, and their composites with BSA are also studied. It is speculated that nanoparticles are first formed in aqueous BSA solution, attributed to the overlapping of hydration layers and autoassembly of inner hydrophobic cores of BSA globular molecules. Nanoprecipitation and soaking evaporation approaches are then used to load curcumin into the BSA scaffolds, followed by cross-linking with glutaraldehyde vapor to improve stability in an aqueous medium. The controlled release of curcumin is demonstrated, paving the way for various hydrophobic drugs loaded into this biodegradable and nonimmunogenic protein scaffold for potential treatments of diverse diseases.