Interfacial behavior of PEGylated lipids and their effect on the stability of squalenoyl-drug nanoassemblies.

Squalenoyl-gemcitabine (Sq-Gem) and squalenoyl-dideoxycytidine (Sq-ddC) are amphiphilic prodrugs that self-assemble in water to form nanoassemblies (NAs) with well-defined structures and size. However, like other drug nanocarriers, these nanoassemblies are rapidly cleared from the blood stream by the reticulo-endothelial system. By adding squalenoyl-PEG (Sq-PEG) or cholesterol-PEG (Chol-PEG) to the squalenoyl prodrugs, composite nanoassemblies (CNAs) were formed, with different sizes and structures.

Anti-HIV efficacy and biodistribution of nucleoside reverse transcriptase inhibitors delivered as squalenoylated prodrug nanoassemblies.

Due to their hydrophilic nature, most nucleoside reverse transcriptase inhibitors (NRTIs) display a variable bioavailability after oral administration and a poor control over their biodistribution, thus hampering their access to HIV sanctuaries. The limited cellular uptake and activation in the triphosphate form of NRTIs further restrict their efficacy and favour the emergence of viral resistance. We have shown that the conjugation of squalene (sq) to the nucleoside analogues dideoxycytidine (ddC) and didanosine (ddI) leads to amphiphilic prodrugs (ddC-sq and ddI-sq) that spontaneously self-organize in water as stable nanoassemblies of 100-300 nm.