in-situ forming composite using PLGA-PEG-PLGA with in-situ forming implant using PLGA: In-vitro , ex-vivo , and in-vivo evaluation of naltrexone release

摘要

Anin-situforming composite (ISFC) of naltrexone (NTX) was prepared using PLGA-PEG-PLGA (triblock) and N-methyl-2-pyrrolidone (NMP) for decreasing the initial burst release. The supercritical CO2method was used to achieve the ring-opening polymerization of the triblock. The Box-Behnken design was used to achieve the minimal initial burst release of NTX in thein-vitrorelease medium.In-vitro,ex-vivo, andin-vivostudies of the ISFC were compared withan in-situforming implant (ISFI) composed of copolymer PLGA 504H. The equivalency of ISFC and Vivitrol?were compared by sampling the concentration of NTX in rabbit blood. The results of thein-vitrorelease evaluation showed that the initial burst release for the ISFC (5.69?±?0.27%) was significantly lower than that for the ISFI (17.45?±?1.07%). The Cmaxof NTX (15.16?±?2.46?ng/mL) from the ISFC was significantly (p?