The Impacts of PLGA/PEG Triblock Copolymers with Variable Molecular Weights on the Sustained Release of Buprenorphine

Objective: Current in-situ injectable implants of buprenorphine (BP) such as Sublocade^®consist of N-methyl-2-pyrrolidone (NMP)-dissolved PLGA. To control the initial burst release ofSublocade^® during the first 24 hours after injection, we here used a BP in-situ forming composite(ISFC) employing different molecular weights of PLGA-PEG-PLGA triblock. Methods: The triblock was synthesized by Ring-Opening Polymerization (ROP) using PEGmolecules with weights of 1500, 3000, and 4000 Da via the melting method. The specifications ofthe triblocks were evaluated by ¹H-NMR, FTIR, GPC, and DSC. The sol-gel, gel-precipitate temperatures,in-vitro release, and composites morphology, degradation, and toxicity were assessedfor determining the features of ISFC 1500, ISFC 3000, and ISFC 4000 formulations. ROP was performedsuccessfully via the melting method. The yields of all polymerization reactions weregreater than 83.4%. Results: The PEG 1500 triblock showed both sol-gel and gel-precipitate temperatures, but PEG3000 and 4000 only showed a sol-precipitate temperature. The values of initial burst release of BPfrom ISFC 1500, ISFC 3000, and ISFC 4000 were 6.52 ± 0.22%, 12.39 ± 0.61%, and 15.80 ±0.98%, respectively. BP release from the ISFCs wascompleted over three weeks for ISFC 1500 and10 days for ISFC 3000 and ISFC 4000. The composites containing PEG 3000 and PEG 4000 weremore spongy and porous than PEG 1500. The ISFC 1500 delivered a higher cell viability (95.17 ±1.15%) compared with ISFC 3000 (86.37 ± 2.25%) and ISFC 4000 (79.70 ± 3.77%). Conclusion: These results indicated that ISFC 1500 wasbiocompatible and delivered suitable earlyinitial burst reactions compared with ISFC 3000 and 4000 and might be a good candidate for preparingsustained-release formulation of BP.