Silk Fibroin-Based Anastrozole Nanoparticle Loaded in Situ Injectable: Development and Characterization

Abstract

Objective: The study aims to find a suitable method of developing silk fibroin-based anastrozole nanoparticles and formulate in situ injectables by loading the optimized nanoparticle formulation for the sustained release treatment of breast cancer. Methods: The nanoparticles were formulated utilizing two different methods, solvent change and precipitation approach using silk fibroin. Prepared nanoparticles characterized in terms of size, zeta potential, polydispersity, and entrapment efficiency. The chosen optimized formulation (SF-ANS-NPs-1) was subsequently analyzed for compatibility investigations by Fourier-transform infrared spectroscopy (FT-IR), thermal analysis, surface morphology, x-ray diffraction, transmission electron spectroscopy, cumulative drug release, and stability studies as per ICH guidelines. Followed by formulating and evaluating in situ injectable gel using pluronic F-127. Results: A particle size of 181.70±1.3 nm was reported by the optimized SF-ANS-NPs-1 formulation. FT-IR and thermal studies confirmed the compatibility of the drug with the polymers, and x-ray diffraction studies indicated crystalline nature. Surface morphology analysis indicated nano-size particle formation. A cumulative drug release (%CDR) of 94.15% was noted at the 168th hour. The results of the stability studies were indicated to be consistent over 90 d. In situ gel formulation showed desired spreadability, sol-gel transition temperature (37±0.5 ℃), viscosity (9.37±1.2 mPa·s), desired acidic pH, and a sustained release for 21 d (98.11%) with three months accelerated stability. Conclusion: The results suggested that the combination of anastrozole with silk fibroin in the form of nanoparticles and in situ gelling systems could be an undoubtedly effective delivery method for prolonging breast cancer therapy.