Thymopentin (TP5) is an effective immunomodulatory agent for autoimmune disease that has been used clinically for decades. However, its application is greatly limited by its extremely short half-life in vivo, poor membrane permeability and extensive metabolism in gastrointestinal tract, resulting in repeated injection and poor patient compliance. In the present study, we developed a TP5-loaded, phospholipid-based phase separation gel (PPSG) to achieve sustained drug release profile and long-lasting therapeutic effects. We firstly demonstrated the physiochemical characteristics of PPSG before and after phase transition by examining the viscosity and morphology change caused by the phase transition. Moreover, the PPSG exerted a low cytotoxicity in L929 cells and HUVECs, suggesting the biocompatibility of PPSG. A month-long drug release profile of TP5 PPSG was observed both in vitro and in vivo, revealing its sustained and controlled drug release property. Most importantly, in cyclophosphamide-induced immunosuppressive rats, a single dose of TP5 PPSG (15 mg/kg, sc) injected could normalize their T-SOD levels and CD4+/CD8+ ratio; such an immunoregulatory effect was comparable to that produced by repeated injection of TP5 solution (0.6 mg/kg per day, sc) for 14 consecutive days. Thus, TP5 PPSG has a great potential for sustained delivery of TP5 in clinical use because of its simple manufacture process, good biocompatibility and long-lasting immunomodulatory efficacy, which could greatly improve patient compliance.

中文翻译：

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具有持久免疫调节作用的负载胸腺素的磷脂基相分离凝胶：体外和体内研究。

胸腺五肽（TP5）是一种针对自身免疫疾病的有效免疫调节剂，已在临床上使用了数十年。但是，它的应用受到其体内半衰期极短，膜通透性差和胃肠道广泛代谢的极大限制，导致重复注射和患者依从性差。在本研究中，我们开发了一种加载了TP5的磷脂基相分离凝胶（PPSG），以实现持续的药物释放曲线和持久的治疗效果。我们首先通过研究相变引起的粘度和形态变化，证明了相变前后PPSG的理化特性。此外，PPSG对L929细胞和HUVEC的细胞毒性较低，提示PPSG具有生物相容性。TP5 PPSG在体外和体内均观察到一个月的药物释放曲线，揭示了其持续和受控的药物释放特性。最重要的是，在环磷酰胺诱导的免疫抑制大鼠中，单剂量注射的TP5 PPSG（15 mg / kg，皮下注射）可以使其T-SOD水平和CD4 + / CD8 +比值正常化。这种免疫调节作用与连续14天重复注射TP5溶液（每天0.6 mg / kg，皮下注射）产生的免疫调节作用相当。因此，TP5 PPSG的制造过程简单，良好的生物相容性和长效的免疫调节功效，在临床上具有持续交付TP5的巨大潜力，可以极大地提高患者的依从性。在环磷酰胺诱导的免疫抑制大鼠中，单次注射TP5 PPSG（15 mg / kg，皮下注射）可以使其T-SOD水平和CD4 + / CD8 +比值正常化。这种免疫调节作用与连续14天重复注射TP5溶液（每天0.6 mg / kg，皮下注射）产生的免疫调节作用相当。因此，TP5 PPSG的制造过程简单，良好的生物相容性和长效的免疫调节功效，在临床上具有持续交付TP5的巨大潜力，可以极大地提高患者的依从性。在环磷酰胺诱导的免疫抑制大鼠中，单次注射TP5 PPSG（15 mg / kg，皮下注射）可以使其T-SOD水平和CD4 + / CD8 +比值正常化。这种免疫调节作用与连续14天重复注射TP5溶液（每天0.6 mg / kg，皮下注射）产生的免疫调节作用相当。因此，TP5 PPSG的制造过程简单，良好的生物相容性和长效的免疫调节功效，在临床上具有持续交付TP5的巨大潜力，可以极大地提高患者的依从性。