AIDS (acquired immune deficiency syndrome), an infection by the human immune deficiency viruses HIV 1 or 2, is mainly caused by infection of the T-helper cells and a subsequent breakdown of the immune system. While these cells die after infection, the virus can very well survive a number of other cells in the body, especially in macrophages. Since the macrophages easily take up nanoparticles, they are ideal delivery systems of anti-HIV drugs into these cells. The uptake of a variety of nanoparticles by HIV-infected and noninfected human macrophages was demonstrated in vitro [171, 187]. The uptake was even significantly higher in infected than in noninfected cells. No difference was observable between macrophages from infected patients and artificially in vitro infected cells . Uptake also was influenced by the surface properties of the nanoparticles .
With the nucleoside analogs azidothymidine (AZT) and dideoxycytidine, the enhanced macrophage uptake only led to a small decrease in virus replication in vitro (macrophage cultures) because these drugs easily penetrate across cell membranes and get access to the cell interior . In contrast, anti-HIV drugs such as the protease inhibitor saquinavir possess no or a very limited cell membrane permeability. Consequently this drug was already in vitro 10 to 20 times more efficient after binding to nanoparticles than with free drug or with a simple mixture of nanoparticles and free drug .
However, even with the drugs like AZT etc. that are able to penetrate cell membranes, binding to nanoparti-cles represents a major advantage. Cell cultures such as the macrophage cultures described above in most cases consist only of one cell type. The body, however, consists of numerous different cell types. Consequently, after intravenous injection to rats AZT bound to nanoparticles accumulated in the organs and cells of the RES that represented reservoirs for HIV, and, as a result, tissue concentrations in these organs were up to 20 times higher than with free drug [85, 86, 350]. Even after oral administration an enhanced uptake of nanoparticle bound drug AZT into these organs was observed .
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