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Anhydrous reverse micelle lecithin nanoparticles/PLGA composite microspheres for long-term protein delivery with reduced initial burst

Longkai Chen,Liling Mei,Disang Feng,Di Huang,Xin Tong,Xin Pan,Chune Zhu,Chuanbin Wu

To address the issue of initial burst release from poly (lactic-co-glycolic) acid (PLGA) microspheres prepared by water-in-oil-in-water (W/O/W) double emulsion technique, PLGA composite microspheres containing anhydrous reverse micelle (ARM) lecithin nanoparticles were developed by a modified solid-in-oil-in-water (S/O/W) technique. Bovine serum albumin (BSA) loaded ARM lecithin nanoparticles, which were obtained by initial self-assembly and subsequent lipid inversion of the lecithin vesicles, were then encapsulated into PLGA matrix by the S/O/W technique to form composite microspheres. In vitro release study indicated that BSA was slowly released from the PLGA composite microspheres over 60 days with a reduced initial burst (11.42 ± 2.17% within 24 h). The potential mechanism of reduced initial burst and protein protection using this drug delivery system was analyzed through observing the degradation process of carriers and fitting drug release data with various kinetic models. The secondary structure of encapsulated BSA was well maintained through the steric barrier effect of ARM lecithin nanoparticles, which avoided exposure of proteins to the organic solvent during the preparation procedure. In addition, the PLGA composite microspheres exhibited superior biocompatibility without notable cytotoxicity. These results suggested that ARM lecithin nanoparticles/PLGA composite microspheres could be a promising platform for long-term protein delivery with a reduced initial burst.