Protein Nanospheres\nand Nanofibers Prepared by Ice-Templating\nfor the Controlled Release of Hydrophobic Drugs

Protein scaffolds play a vital role in drug delivery\nsystems. However,\nfew research studies have been focused on loading hydrophobic drugs\non protein scaffolds in biomedical fields. Here, we report on the\ndevelopment of protein microspheres and nanofibers by a simple ice-templating\napproach and their use as scaffolds for the controlled release of\nhydrophobic drugs, with bovine serum albumin (BSA) as the model protein\nand curcumin as the model hydrophobic drug. The BSA scaffolds display\nthe unique nanofibrous and microspherical structures. This is a surprising\ndiscovery because there has been no report on the formation of microspheres\nvia simple ice-templating of solutions or suspensions. To further\nunderstand the formation of microspheres by this approach, lysozyme,\npapain, and their composites with BSA are also studied. It is speculated\nthat nanoparticles are first formed in aqueous BSA solution, attributed\nto the overlapping of hydration layers and autoassembly of inner hydrophobic\ncores of BSA globular molecules. Nanoprecipitation and soaking evaporation\napproaches are then used to load curcumin into the BSA scaffolds,\nfollowed by cross-linking with glutaraldehyde vapor to improve stability\nin an aqueous medium. The controlled release of curcumin is demonstrated,\npaving the way for various hydrophobic drugs loaded into this biodegradable\nand nonimmunogenic protein scaffold for potential treatments of diverse\ndiseases.