Silk fibroin as a biomaterial for drug delivery: From gland to clinic

Silk fibroin (SF), a natural protein characterized by favorable mechanical properties, tunable biodegradation, and intrinsic biocompatibility, has emerged as a versatile platform for drug delivery systems (DDS). Unlike the published reviews, most of which have mainly described SF merely as a passive post-extraction carrier, this review presents a holistic “Gland to Clinic” perspective. It systematically addresses existing knowledge gaps by elucidating the physicochemical and biological properties of SF as a molecular framework for DDS design and fabrication. The progression of SF from a raw biopolymer produced in the gland to a functional biomaterial as a drug carrier for clinical applications is outlined, emphasizing advanced extraction techniques and chemical or genetic modifications that enhance its potential for controlled drug release. By highlighting the latest advancements in SF-based DDS and consolidating its role as an adaptable platform, this review provides an integrated perspective on the development and clinical translation of these systems. Finally, it summarizes the current challenges that remain and proposes potential solutions to address them.