Department of Chemistry, Northwestern University, Evanston, Illinois, USA.
J Liposome Res. 2011 Jun;21(2):106-15. doi: 10.3109/08982104.2010.483597. Epub 2010 May 21.
In this article, a novel delivery system for the anticancer drug, arsenic trioxide (ATO), is characterized. The release of ATO from DPPC liposomes with MPPC lysolipid incorporated into the bilayer was measured. Upon heating the liposomes to 37°C, there was a 15-25% release over 24 hours. The ATO release from the DPPC and DPPC:MPPC (5%) systems leveled off after 10 hours at 37°C, whereas the DPPC:MPPC (10%) liposomes continue to release ATO over the 24-hour time span. Upon heating the liposomes rapidly to 42°C, the release rate was substantially increased. The systems containing lysolipids exhibited a very rapid release of a significant amount of arsenic in the first hour. In the first hour, the DPPC:MPPC (5%) liposomes released 40% of the arsenic and the DPPC:MPPC (10%) liposomes released 55% of the arsenic. Arsenic release from pure DPPC liposomes was comparable at 37 and 42°C, indicating that the presence of a lysolipid is necessary for a significant enhancement of the release rate. A coarse-grained molecular dynamics (CGMD) model was used to investigate the enhanced permeability of lysolipid-incorporated liposomes and lipid bilayers. The CG liposomes did not form a gel phase when cooled due to the high curvature; however, permeability was still significantly lower below the liquid-to-gel phase-transition temperature. Simulations of flat DPPC:MPPC bilayers revealed that a peak in the permeability did coincide with the phase transition from the gel to LC state when the lysolipid, MPPC, was present. No pores were observed in the simulations, so it is unlikely this was the permeability-enhancing mechanism.
本文介绍了一种新型的抗癌药物三氧化二砷（ATO）的递药系统。研究了将 MPPC 溶血磷脂酰胆碱掺入双层中的 DPPC 脂质体中 ATO 的释放情况。将脂质体加热至 37°C 时，在 24 小时内有 15-25%的 ATO 释放。在 37°C 下，10 小时后 DPPC 和 DPPC:MPPC（5%）系统中的 ATO 释放趋于平稳，而 DPPC:MPPC（10%）脂质体在 24 小时内持续释放 ATO。当脂质体迅速加热至 42°C 时，释放率大大增加。含有溶血磷脂酰胆碱的系统在第一小时内迅速释放出大量的砷。在第一小时内，DPPC:MPPC（5%）脂质体释放了 40%的砷，DPPC:MPPC（10%）脂质体释放了 55%的砷。在 37°C 和 42°C 下，纯 DPPC 脂质体的砷释放情况相当，表明溶血磷脂酰胆碱的存在对于显著提高释放率是必要的。使用粗粒化分子动力学（CGMD）模型研究了溶血磷脂酰胆碱掺入脂质体和脂质双层的增强渗透性。由于曲率高，CG 脂质体在冷却时不会形成凝胶相；然而，在低于凝胶到液晶相转变温度时，渗透性仍然显著降低。DPPC:MPPC 双层的模拟表明，当存在溶血磷脂酰胆碱 MPPC 时，渗透性的峰值确实与从凝胶到 LC 状态的相变相吻合。模拟中没有观察到孔，因此不太可能是这种增强渗透性的机制。
