PEGylated biodegradable nanoparticles based on poly(alkyl cyanoacrylate) polymers have been investigated to encapsulate didanosine prodrugs as an approach to treat HIV-1 associated dementia. To achieve this goal, an amphiphilic poly[(poly(ethylene glycol) cyanoacrylate)-co-(hexadecyl cyanoacrylate)] (PEGCA-PHDCA) copolymer has been synthesized and two different didanosine prodrugs have been used; the dipalmitoyl glycerol didanosine (ProddINP) and the dipalmitoyl glycerol phosphate didanosine (ProddIP), only differ by the presence or not of a phosphate group in their chemical structure. By means of differential scanning calorimetry (DSC), the capacity of PEGCA-PHDCA copolymer to incorporate ProddINP and ProddIP prodrugs was investigated. PEGCA-PHDCA nanoparticles were then prepared via an optimised solvent emulsion/evaporation technique using the incorporation ratios determined by DSC. Finally, confocal laser scanning microscopy experiments have shown these prodrugs-loaded nanoparticles were uptaken by rat immortalised brain endothelial cells (SV-ARBEC). These first results appeared promising for further in vitro and in vivo evaluation of these nanoparticles.
Journal of Nanoneuroscience1, no. 2 (December 2009): 174–183.