Abstract
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 144 h 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.
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