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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.

Objective: An injectable long acting In-Situ Forming Gel (ISFG) of human Growth Hormone (hGH) was prepared by using triblock PCL-PEG-PCL (Mw 1500-1500-1500). Ring-Opening Polymerization (ROP) of triblock using microwave was applied. Methods: The BCA protein assay Kit was used to determine the concentration of hGH in the in-vitro release medium. Finally, Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) tests and Circular Dichroism (CD) spectrum were done to approve the stability of released hGH. The result of ROP demonstrated that the proportion of PCL to PEG accorded with the initial molar ratio of the monomers. The cross-section of the Surface Electron Microscopy (SEM) indicated the porous framework of the hydrogel could load the drug into its tridimensional matrixes structure. There is the low initial burst release of hGH from the supramolecular hydrogel. Results: The maximum in-vitro release of hGH was 71.2 % ± 1.5 that were due to hGH degrading after this time (21 days). The CD spectrum and SDS-PAGE results confirmed the stability of hGH during invitro release evaluation. Conclusion: The results suggest that the sustained-release formulation using PCL-PEG-PCL can be applied to control the release of hGH.