Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Pharm Res. 2012 Dec;29(12):3475-85. doi: 10.1007/s11095-012-0843-0. Epub 2012 Aug 21.
Pluronic F-127 (PF127) has previously shown to prolong the sustained release of various proteinous drugs and their serum half-lives. Subsequently, we have extended this approach to look at in vitro release, in vivo efficacy and pharmacokinetics of interleukin-1 receptor antagonist (IL-1Ra).
Various concentrations of PF127 gels were prepared using cold method. In vitro drug release kinetic studies were performed using membraneless dissolution method. Stability of IL-1Ra was assessed by SDS-PAGE. In vivo studies and in vivo bioactivity of IL-1Ra were also performed on wistar rats.
IL-1Ra loaded PF127 gels showed in vitro sustained release of IL-1Ra, depending on the concentration of gel used. SDS-PAGE confirmed the stability of protein during its in vitro release. PF127 gel also exhibited prolonged release of IL-1Ra in rats as compared to that of IL-1Ra aq. solution. In vivo bioactivity of IL-1Ra loaded in gel was confirmed by its ability to inhibit IL-1β-stimulated induction of IL-6.
When compared directly, IL-1Ra loaded PF127 gel exhibited prolonged in vitro and in vivo release, greater efficacy to induce hypoglycemia and inhibited IL-1β-stimulated production of IL-6 as compared to IL-1Ra aq. solution. We believe that this methodology for sustained delivery of IL-1Ra probably be suitable for the convenience of patients to achieve desired therapeutic potentials without exceeding dose limits and frequent administration.
聚氧乙烯（20）山梨醇酐单月桂酸酯（PF127）先前已被证明能延长各种蛋白质类药物的持续释放时间及其血清半衰期。随后，我们采用这种方法来研究白细胞介素-1 受体拮抗剂（IL-1Ra）的体外释放、体内疗效和药代动力学。
采用冷法制备不同浓度的 PF127 凝胶。采用无膜溶解法进行体外药物释放动力学研究。通过 SDS-PAGE 评估 IL-1Ra 的稳定性。还在 Wistar 大鼠上进行了 IL-1Ra 的体内研究和体内生物活性研究。
IL-1Ra 负载的 PF127 凝胶表现出 IL-1Ra 的体外持续释放，这取决于所使用的凝胶浓度。SDS-PAGE 证实了蛋白质在体外释放过程中的稳定性。与 IL-1Ra aq. 溶液相比，PF127 凝胶还表现出 IL-1Ra 的延长释放。通过其抑制 IL-1β 刺激诱导的 IL-6 产生的能力，证实了载有 IL-1Ra 的凝胶的体内生物活性。
当直接比较时，与 IL-1Ra aq. 溶液相比，负载有 IL-1Ra 的 PF127 凝胶表现出延长的体外和体内释放、更大的诱导低血糖效力，并抑制了 IL-1β 刺激产生的 IL-6。我们相信，这种用于持续释放 IL-1Ra 的方法可能适合患者的便利性，以实现所需的治疗潜力，而不会超过剂量限制和频繁给药。
