顺铂新型脂质体制剂的制备与评价
Preparation and evaluation of a novel liposomal formulation of cisplatin.
作者信息
Zhou Xiaoju, Wang Jiong, Wu Jianhong, Yang Xiaojuan, Yung Bryant C, Lee L James, Lee Robert J
机构信息
State Key Laboratory of Virology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, PR China; Division of Pharmaceutics, The Ohio State University, Columbus, OH 43210, United States.
Wuhan Grand Hoyo Pharmaceutical Co., Ltd, Wuhan 430074, PR China.
出版信息
Eur J Pharm Sci. 2015 Jan 23;66:90-5. doi: 10.1016/j.ejps.2014.10.004. Epub 2014 Oct 16.
A novel liposomal formulation of cisplatin (L-CDDP) was synthesized and characterized. The L-CDDP was formed by conjugating CDDP to the carboxyl of oleic acid incorporated into empty liposomes. Particle size (155.4±16.1nm) and zeta potential (-50.92±1.19mV) of the L-CDDP were determined. In addition, pharmacokinetic properties and antitumor activity in vitro and in vivo were evaluated. Pharmacokinetic study demonstrated that L-CDDP had markedly prolonged circulation time relative to the free drug. Furthermore, L-CDDP showed significantly enhanced in vitro cytotoxicity in comparison to free CDDP. A549-engrafted mice treated with L-CDDP had a higher survival rate compared to those treated with free CDDP. Finally, A549-engrafted mice treated with L-CDDP showed no significant loss of body weight, whereas free CDDP treatment at the same dose caused significant loss of body weight. These results suggest further evaluation of the in vivo antitumor efficacy of the novel L-CDDP formulation is warranted.
合成并表征了一种新型的顺铂脂质体制剂（L-CDDP）。L-CDDP是通过将顺铂与掺入空脂质体中的油酸羧基共轭形成的。测定了L-CDDP的粒径（155.4±16.1nm）和zeta电位（-50.92±1.19mV）。此外，还评估了其药代动力学性质以及体内外抗肿瘤活性。药代动力学研究表明，相对于游离药物，L-CDDP的循环时间显著延长。此外，与游离顺铂相比，L-CDDP在体外的细胞毒性显著增强。与接受游离顺铂治疗的小鼠相比，接受L-CDDP治疗的A549移植瘤小鼠具有更高的存活率。最后，接受L-CDDP治疗的A549移植瘤小鼠体重没有明显减轻，而相同剂量的游离顺铂治疗则导致体重显著减轻。这些结果表明，有必要进一步评估新型L-CDDP制剂的体内抗肿瘤疗效。
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