SILK FIBROIN NANOPARTICLES AS DRUG DELIVERY SYSTEMS: FABRICATION METHODS, PHYSICOCHEMICAL PROPERTIES, DRUG LOADING MECHANISMS, AND BIOMEDICAL APPLICATIONS

Abstract

Background: Silk fibroin (SF)—the structural protein constituting approximately 70–80% of Bombyx mori silk cocoon—has emerged as a leading biomaterial for drug delivery nanoparticle formulation owing to its exceptional biocompatibility, biodegradability, tunable mechanical properties, diverse functional surface chemistry, and FDA-approved status. SF nanoparticles (SF-NPs) can encapsulate hydrophobic and hydrophilic therapeutics, proteins, nucleic acids, and imaging agents, providing controlled and sustained release profiles through both diffusion-mediated and biodegradation-mediated mechanisms. Uzbekistan, as one of the world's largest silk-producing nations, possesses a unique strategic advantage in silk-based biomaterial research and development.

Objective: To provide a concise, evidence-based review of the molecular structure of silk fibroin and its physicochemical basis for drug encapsulation, the principal SF-NP fabrication methods and their comparative performance, drug loading and release mechanisms, surface functionalization strategies for targeted delivery, and current biomedical applications in cancer therapy, wound healing, and protein biologics delivery.

Methods: A systematic review of eight primary peer-reviewed sources—original research articles, comprehensive biomaterial reviews, and authoritative drug delivery studies published between 2001 and 2024—was conducted.

Results: SF-NPs prepared by desolvation, nanoprecipitation, and self-assembly yield particle diameters of 50–400 nm with PDI < 0.2 and drug encapsulation efficiencies of 55–95%. Beta-sheet crystallinity induced by methanol treatment or lyophilization reduces drug release rate by 3–5-fold compared to amorphous SF matrices. Surface conjugation of targeting ligands (folic acid, RGD peptide, transferrin) improves cancer cell uptake by 3–8-fold in vitro. SF-NPs demonstrate in vivo biocompatibility with no significant immune response or organ toxicity at doses up to 200 mg/kg in rodent models.

Conclusion: Silk fibroin nanoparticles represent a versatile, biocompatible, and chemically tunable platform for precision drug delivery. Their programmable beta-sheet crystallinity, facile surface functionalization, and Uzbekistan's abundant native silk feedstock make SF-NP technology a scientifically compelling and economically strategic research priority for the country's pharmaceutical and biomedical materials sector.