A patient-friendly delivery system to release human growth hormone (hGH) is very desirable. In situ forming implant systems (ISIs) can provide a long acting and effective protein delivery. In these systems, solvents and additives play major roles in drug release. In this study, four groups of PLGA-based ISIs containing hGH were prepared in N-methyl-2-pyrrolidone (NMP) and poly(ethylene glycol) dimethyl ether (PEG-DME) as solvents with and without tris(hydroxymethyl) aminomethane (Tris) as stabilizer. Several analyses were used to investigate the implants, which include release profile, viscosity, contact angle, gel permeation chromatography (GPC), scanning electron microscopy (SEM), hGH and IGF-1 serum measurements and histopathology. In in vitro release experiments, the hGH cumulative release from PEG-DME system was twice that from NMP system during 14 days, and hGH release was tripled in the presence of Tris. With the addition of Tris to the ISIs containing PEG-DME, the water penetration, interconnectivity of pores and inner channels, surface pores and hydrophilicity were increased. Moreover, the effect of Tris on the hGH stabilization synergized its positive effects and increased the hGH final cumulative release. Results of the ISIs containing PEG-DME and Tris injection in rabbits demonstrated a reduced tissue inflammation. Moreover, the 14-days serum levels of the hGH and IGF-1 of this system in recipient rabbits were comparable to those of the commercial daily injection samples.

非常需要患者友好的释放人生长激素（hGH）的递送系统。原位形成植入系统（ISI）可提供长效且有效的蛋白质输送。在这些系统中，溶剂和添加剂在药物释放中起主要作用。在这项研究中，在N中制备了四组含hGH的基于PLGA的ISI-甲基-2-吡咯烷酮（NMP）和聚（乙二醇）二甲醚（PEG-DME）作为溶剂，有和没有三（羟甲基）氨基甲烷（Tris）作为稳定剂。使用了几种分析方法来研究植入物，包括释放曲线，粘度，接触角，凝胶渗透色谱法（GPC），扫描电子显微镜（SEM），hGH和IGF-1血清测量值以及组织病理学。在体外释放实验中，在14天中，PEG-DME系统的hGH累积释放是NMP系统的hGH累积释放的两倍，在存在Tris的情况下，hGH的释放量增加了两倍。通过向含有PEG-DME的ISI中添加Tris，水的渗透性，孔与内部通道的互连性，表面孔和亲水性得到了提高。此外，Tris对hGH稳定的作用与其正作用协同作用，并增加了hGH的最终累积释放。包含PEG-DME和Tris注射液的ISI的兔子结果显示组织炎症减轻。此外，在受体兔子中该系统的14天血清hGH和IGF-1的血清水平与每日商业注射样品相当。