Preparation of uniform-sized GeXIVA[1,2]-loaded PLGA microspheres as long-effective release system with high encapsulation efficiency.

The purpose of this study was to prepare GeXIVA[1,2] PLGA microspheres by W/O/W re-emulsification-solvent evaporation technology and to develop sustained-release formulations to meet the clinical treatment needs of chronic neuropathic pain. Through prescription optimization, the uniformity of particle size and the encapsulation efficiency is improved, so as to achieve the quality standard of the microspheres. The mechanism of trehalose improving the stability of GeXIVA[1,2] was studied and verified by molecular simulation. The results showed that when adding trehalose to W1, using the PLGA model of 75:25, PLGA concentration of 30%, PVA concentration of 1.5%, adding 1% NaCl to PVA and adding 1% NaCl to solidification water, the prepared microspheres are smooth, the particle size is about 25 μm, and the encapsulation rate reaches 90%. The results of in vitro release experiments showed that the microspheres could be released steadily for about 30 days. The microsphere samples were characterized and analyzed by molecular simulation and powder X-ray diffractometer, and the protective mechanism of trehalose on GeXIVA[1,2] was discussed. The results showed that the hydrogen bond formed between trehalose and GeXIVA[1,2] acted as a hydration film and played a certain protective role on GeXIVA[1,2]. In addition, high-viscosity trehalose can form a glass state and wrap around GeXIVA[1,2], reducing the free movement of molecules. In the microsphere system, trehalose can also avoid the influence of PLGA material on the secondary structure of GeXIVA[1,2]. In conclusion, this study is expected to provide a new therapeutic strategy for the treatment of chronic neuropathic pain.