Development of silk fibroin modified poly(l-lactide)–poly(ethylene glycol)–poly(l-lactide) nanoparticles in supercritical CO2

• The SEDS process was used to prepare SF/PLLA–PEG–PLLA nanoparticles.
• SF and PLLA–PEG–PLLA became more amorphous after the SEDS process.
• Incorporating SF into PLLA–PEG–PLLA nanoparticles improved biocompatibility.
• Incorporating SF into PLLA–PEG–PLLA nanoparticles enhanced cellular uptake.

Silk fibroin (SF) modified poly(l-lactide)–poly(ethylene glycol)–poly(l-lactide) (SF/PLLA–PEG–PLLA) nanoparticles were successfully fabricated in a process of solution-enhanced dispersion by supercritical CO2 (SEDS). The SF/PLLA–PEG–PLLA nanoparticles exhibited a composite structure with mean particle size of 634 nm and silk fibroin wrapped with PLLA–PEG–PLLA triblock polymer. Fourier transform infrared spectroscopy (FTIR) measurement indicated that minor secondary structural changes of silk fibroin occurred after the SEDS process. X-ray powder diffraction (XRPD) analysis supported the results of FTIR measurement and also revealed that the SEDS process resulted in a notable decrease in crystallinity of the PLLA–PEG–PLLA. In vitro cytotoxicity evaluation by MTS assay indicated that SF/PLLA–PEG–PLLA nanoparticles exhibited better biocompatibility than PLLA–PEG–PLLA nanoparticles. Fluorescence microscopy observation and flow cytometric analysis suggested that SF/PLLA–PEG–PLLA nanoparticles could be internalized into fibroblasts in a time-dependent manner and also possessed faster cell adhesion and internalization ability than PLLA–PEG–PLLA nanoparticles. In conclusion, SF/PLLA–PEG–PLLA nanoparticles prepared by the SEDS process could be used as potential biomaterials in the biomedical field, especially nanoparticle drug delivery systems.

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