Purpose

In situ-forming gels (semi-solid state) (ISFGs) are widely used as sustained drug delivery, but they show a high burst release as well. The purpose of the current study is to make triblock that can make a quick gel on injection with a minimum burst release.

Methods

In this study, to control the release of levothyroxine from ISFG, PLGA-PEG-PLGA (triblock) polymer was used. The melting method was employed to synthesize the triblock via ring-opening polymerization (ROP). Different weight percentages of triblock in the formulation were investigated to reach the minimum initial burst release of levothyroxine from ISFGs. Furthermore, the results of the in-situ forming implant (solid-state) (ISFI) of levothyroxine prepared from PLGA 504 H polymers were compared with ISFG.

Results

The melting method employed in this study showed a successful ROP of the triblock. As the % triblock concentration was increased from 30 to 50%, the initial burst release decreased significantly. The initial burst release levothyroxine from ISFG (6.52 ± 0.30%) was much lower than the amount of levothyroxine released from ISFI (14.15 ± 0.79%). No cytotoxicity was observed for the sustained-release formulation containing ISFG 50% according to the MTT assay.

Conclusion

The results indicated that this formulation was safe to be administered subcutaneously. As the synthesized triblock has thermosensitive properties, and also has the hydrogen bonding between the N-methyl pyrrolidone molecules and PEG, therefore, these properties make ISFG formulation to have a smaller initial burst release compared to ISFI formulation.

中文翻译：

---

使用PLGA-PEG-PLGA的左甲状腺素注射剂可持续释放的优化和体外评估

目的

原位形成的凝胶（半固态）（ISFG）被广泛用作持续药物输送，但它们也显示出高的突释释放。当前研究的目的是制造可以在注射时产生快速凝胶且释放量最小的三嵌段共聚物。

方法

在这项研究中，为了控制左甲状腺素从ISFG的释放，使用了PLGA-PEG-PLGA（三嵌段）聚合物。采用熔融方法通过开环聚合（ROP）合成三嵌段。研究了配方中三嵌段化合物的不同重量百分比以达到从ISFGs中最小的左甲状腺素初始爆发释放。此外，将由PLGA 504 H聚合物制备的左甲状腺素的原位形成植入物（固态）（ISFI）的结果与ISFG进行了比较。

结果

本研究中使用的熔融方法显示出三嵌段的成功ROP。随着三嵌段化合物的百分比浓度从30％增加到50％，初始突释释放显着降低。ISFG的初始突发性释放左甲状腺素（6.52±0.30％）远低于从ISFI释放的左甲状腺素（14.15±0.79％）。根据MTT分析，对于包含50％ISFG的持续释放制剂，未观察到细胞毒性。

结论

结果表明该制剂可安全地皮下给药。由于合成的三嵌段具有热敏性质，并且在N-甲基吡咯烷酮分子和PEG之间也具有氢键，因此，这些性质使ISFG制剂与ISFI制剂相比具有较小的初始爆炸释放。