Jain Subheet, Tiwary A K, Jain N K
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, 147002, India.
Curr Drug Deliv. 2008 Oct;5(4):275-81. doi: 10.2174/156720108785915078.
The present study was aimed at in vitro and in vivo evaluation of PEGylated elastic liposomal formulation for lymphatic targeting of zidovudine (AZT). PEGylated elastic liposomal formulation was prepared and characterized for characteristic in vitro, ex-vivo and in vivo parameters. The plain and PEGylated elastic liposomal formulation showed transdermal flux of 99.8+/-5.8 and 119.5+/-5.2 microg/cm(2)/hr, respectively across the rat skin. Results of biodistribution study indicated 27-fold higher accumulation of AZT in lymphoid tissues after application of PEGylated elastic liposomes as compared to free drug. The efficient localization of elastic liposomal formulation in lymphatic system is of particular interest for HIV therapy, taking in account that replication of HIV mainly takes place in the lymphoid system. The Cellular uptake studies showed significantly higher cellular uptake in lymphoid cells (MT-2 cell line) from PEGylated elastic liposomal formulation (88.9+/-8.7%) in comparison to phosphate buffer saline (PBS, pH 7.4) solution of drug (27.1+/-2.8%). The entrapment of AZT into PEGylated elastic liposomes represents a potential approach for overcoming the toxicity by its selective uptake in lymphoid organs. This represents attractive approach for sustained and targeted delivery of AZT.
本研究旨在对用于齐多夫定（AZT）淋巴靶向的聚乙二醇化弹性脂质体制剂进行体外和体内评价。制备了聚乙二醇化弹性脂质体制剂，并对其体外、离体和体内特征参数进行了表征。普通和聚乙二醇化弹性脂质体制剂在大鼠皮肤上的透皮通量分别为99.8±5.8和119.5±5.2微克/平方厘米/小时。生物分布研究结果表明，与游离药物相比，应用聚乙二醇化弹性脂质体后，AZT在淋巴组织中的蓄积量高出27倍。考虑到HIV主要在淋巴系统中复制，弹性脂质体制剂在淋巴系统中的有效定位对于HIV治疗尤为重要。细胞摄取研究表明，与药物的磷酸盐缓冲盐水（PBS，pH 7.4）溶液（27.1±2.8%）相比，聚乙二醇化弹性脂质体制剂（88.9±8.7%）在淋巴样细胞（MT-2细胞系）中的细胞摄取显著更高。将AZT包封到聚乙二醇化弹性脂质体中是通过其在淋巴器官中的选择性摄取来克服毒性的一种潜在方法。这是一种用于AZT持续靶向递送的有吸引力的方法。
