Silk Protein-Based Nanoporous Microsphere for Controllable Drug Delivery through Self-Assembly in Ionic Liquid System.

Abstract

Ionic liquids (ILs) showed a promising application prospect in the field of biomedicine due to their unique recyclability, modifiability, and structure adjustability. In this study, nanoporous microsphere of silk protein and blending with poly(d,l-lactic acid) as model drug delivery was fabricated, respectively, through an IL-induced self-assembly method. Their morphology, structure, and thermal properties were comparably investigated through scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, differential scanning calorimetry, X-ray diffraction, and thermogravimetric analyses, and the interaction mechanisms were also discussed to elucidate the effect of structure on drug delivery kinetics. The pure protein exhibited a bigger nanopore size in the microsphere compared to the composite one, facilitating more effective drug loading up to 88.7%. However, drug release was over 53.5% for the composite during initial 4 h, while pure protein was only about half of the composite. Both of them exhibited sustained slow release after 24 h and anticancer efficacy. Furthermore, the favorable compatibility between drug and microsphere vehicle was found and experienced improved thermal stability upon encapsulation, which could protect the drug molecules in high temperature at 200 °C. When the protein and its composite self-assembled to microspheres in ILs due to electrostatic and hydrophobic interaction, the drug could be infiltrated into the nanoporous matrix through biophysical action, and the protein structure displayed reversible transition during delivery. The sustained slow release from pure SF was attributed to the high β-sheet block action and strong drug-protein interactions, whose strength could be tuned through blending poly(d,l-lactic acid) with protein. These findings indicated that the SF-based nanoporous microspheres formed from IL self-assembled system are an ideal and potential drug delivery vehicle which can be incorporated into various biomaterials in the future.