Two cholesterol derivative-based PEGylated liposomes as drug delivery system, study on pharmacokinetics and drug delivery to retina
Two cholesterol derivative-based PEGylated liposomes as drug delivery system, study on pharmacokinetics and drug delivery to retina
复制标题
DOI：
10.1088/0957-4484/25/27/275103
复制
发表时间：
2014-07-11
期刊：
影响因子：
3.5
通讯作者：
Wang, Jin-Ye
中科院分区：
文献类型：
--
作者：
Geng, Shengyong;Yang, Bin;Wang, Jin-Ye
本研究合成了两种胆固醇衍生物（4-胆固醇羰基-4 '-（N，N，N-三乙胺丁氧基溴）偶氮苯（CAB）和4-胆固醇羰基-4'-（N，N-二乙胺丁氧基）偶氮苯（ACB），其中一种带正电荷，另一种带中性电荷，并将其与磷脂和胆固醇结合形成阿霉素（DOX）脂质体。通过包括1，2-二硬脂酰基-sn-甘油基-3-磷脂酰乙醇-胺-N-[甲氧基-（聚乙二醇）-2000（DSPE-PEG 2000）实现PEG化。我们的研究结果表明，聚乙二醇修饰的脂质体显示出显着改善的稳定性和药物泄漏减少相比，非聚乙二醇修饰的在体外。大鼠体内研究也显示，当脂质体被PEG化时，DOX的药代动力学和循环半衰期显著改善（p < 0.05）。特别地，与常规PC脂质体和带正电荷的CAB脂质体相比，中性胆固醇衍生物ACB在改善脂质体在体循环中的稳定性方面发挥了一定作用，无论是否具有PEG化。此外，在局部药物递送的情况下，与中性PEG化脂质体相比，带正电荷的PEG-脂质体不仅将更多的药物递送到大鼠视网膜中（p < 0.001），而且还保持更长的药物保留时间。
In this study, two cholesterol derivatives, (4-cholesterocarbonyl-4'-(N, N, N-triethylamine butyloxyl bromide) azobenzene (CAB) and 4-cholesterocarbonyl-4'-(N, N-diethylamine butyloxyl) azobenzene (ACB), one of which is positively charged while the other is neutral, were synthesized and incorporated with phospholipids and cholesterol to form doxorubicin (DOX)-loaded liposomes. PEGylation was achieved by including 1,2-distearoyl-sn-glycero-3-phosphatiylethanol-amine-N-[methoxy-(polyethylene glycol)-2000 (DSPE-PEG2000). Our results showed that PEGylated liposomes displayed significantly improved stability and the drug leakage was decreased compared to the non-PEGylated ones in vitro. The in vivo study with rats also revealed that the pharmacokinetics and circulation half-life of DOX were significantly improved when liposomes were PEGylated (p < 0.05). In particular, the neutral cholesterol derivative ACB played some role in improving liposomes' stability in systemic circulation compared to the conventional PC liposome and the positively charged CAB liposome, with or without PEGylation. In addition, in the case of local drug delivery, the positively charged PEG-liposome not only delivered much more of the drug into the rats' retinas (p < 0.001), but also maintained much longer drug retention time compared to the neutral PEGylated liposomes.