Han Hee Dong, Lee Aeri, Hwang Taewon, Song Chung Kil, Seong Hasoo, Hyun Jinho, Shin Byung Cheol
Bioactive Molecules Delivery and Control Research Team, Korea Research Institute of Chemical Technology, Yuseong, Daejeon, South Korea.
J Control Release. 2007 Jul 31;120(3):161-8. doi: 10.1016/j.jconrel.2007.03.020. Epub 2007 Apr 4.
Polymer incorporation on liposomal membranes has been extensively studied as a method of enhancing the circulation time of liposomes in the bloodstream. In this study, we investigated the in vitro and in vivo characteristics of liposomes whose surface was modified using a comblike polymer comprised of a poly(methyl methacrylate) (PMMA) backbone and short poly(ethylene oxide) (PEO) side chains. Doxorubicin (DOX)-loaded liposomes incorporating with the comblike polymer were prepared and their circulation time, biodistribution and antitumor activity were evaluated in B16F10 melanoma tumor-bearing mice. The circulation half-life time in the bloodstream of the comblike polymer-incorporated liposomes (CPILs) was approximately 14- or 2-fold higher than those of the conventional or polyethyleneglycol-fixed liposomes (PEG-liposomes), respectively. Additionally, in the biodistribution assay, the accumulation of the CPILs in the tumor was higher than those of the other liposomes. Based on this result, the antitumor activities of the CPILs were higher than those of conventional liposome formulation of DOX or free DOX due to the higher passive targeting efficiency of the long-circulating CPILs to tumor. This study suggests that the incorporation of the comblike polymer on the liposomal membrane is a promising tool to further improve circulation time of liposomes in tumor-bearing mice.
作为一种延长脂质体在血液中循环时间的方法，聚合物掺入脂质体膜已得到广泛研究。在本研究中，我们研究了表面用由聚甲基丙烯酸甲酯（PMMA）主链和短聚环氧乙烷（PEO）侧链组成的梳状聚合物修饰的脂质体的体外和体内特性。制备了掺入梳状聚合物的载阿霉素（DOX）脂质体，并在荷B16F10黑色素瘤的小鼠中评估了它们的循环时间、生物分布和抗肿瘤活性。掺入梳状聚合物的脂质体（CPILs）在血液中的循环半衰期分别比传统脂质体或聚乙二醇固定脂质体（PEG-脂质体）高约14倍或2倍。此外，在生物分布试验中，CPILs在肿瘤中的蓄积高于其他脂质体。基于这一结果，由于长循环CPILs对肿瘤的被动靶向效率更高，CPILs的抗肿瘤活性高于阿霉素的传统脂质体制剂或游离阿霉素。本研究表明，在脂质体膜上掺入梳状聚合物是进一步提高荷瘤小鼠脂质体循环时间的一种有前景的工具。
