Dutta Tathagata, Garg Minakshi, Jain Narendra K
Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, M.P. 470003, India.
Eur J Pharm Sci. 2008 Jul 3;34(2-3):181-9. doi: 10.1016/j.ejps.2008.04.002. Epub 2008 Apr 18.
HIV infected macrophages are considered as reservoirs for spreading the virus in AIDS patients. Tuftsin not only binds specifically to the mononuclear phagocytic cells but also enhances their natural killer activity. The purpose of this study is to explore the targeting potential and anti-HIV activity of efavirenz (EFV) loaded, tuftsin conjugated 5th generation poly(propyleneimine) dendrimers (TuPPI) in vitro. Tuftsin was chemically conjugated to 5th generation poly(propyleneimine) dendrimers (PPI). The entrapment efficiency of PPI and TuPPI were found to be 37.43+/-0.3% and 49.31+/-0.33%, respectively. TuPPI was found to slow down and prolong the in vitro release of EFV upto 144h against PPI, which releases the drug completely within 24 h. TuPPI possessed negligible cytotoxicity as compared to that of PPI. The cellular uptake of TuPPI was found to be 34.5 times higher than that of the free drug in first 1 h and was significantly higher in HIV infected macrophages than that of uninfected cells. TuPPI was found to reduce the viral load by 99% at a concentration of 0.625 ng/ml, which is due to the enhanced cellular uptake, reduced toxicity and the inherent anti-HIV activity of TuPPI.
HIV感染的巨噬细胞被认为是艾滋病患者体内病毒传播的储存库。促吞噬素不仅能特异性结合单核吞噬细胞，还能增强其天然杀伤活性。本研究的目的是在体外探索负载依法韦仑（EFV）、缀合促吞噬素的第五代聚（丙烯亚胺）树枝状大分子（TuPPI）的靶向潜力和抗HIV活性。促吞噬素通过化学方法与第五代聚（丙烯亚胺）树枝状大分子（PPI）缀合。发现PPI和TuPPI的包封率分别为37.43±0.3%和49.31±0.33%。与在24小时内完全释放药物的PPI相比，TuPPI能减缓并延长EFV的体外释放长达144小时。与PPI相比，TuPPI的细胞毒性可忽略不计。发现TuPPI在最初1小时内的细胞摄取量比游离药物高34.5倍，且在HIV感染的巨噬细胞中的摄取量显著高于未感染细胞。在浓度为0.625 ng/ml时，TuPPI能将病毒载量降低99%，这归因于其增强的细胞摄取、降低的毒性以及TuPPI固有的抗HIV活性。
