Mannan-coated gelatin nanoparticles for sustained and targeted delivery of didanosine: In vitro and in vivo evaluation
Macrophages of the reticuloendothelial system and brain act as major reservoir for HIV because of their long term survival after HIV infection and ability to spread virus particles to bystander CD4 positive lymphocyte cells. The objective of the present study was to investigate mannan-coated nanoparticles for macrophage targeting of didanosine. Different didanosine loaded nanoparticles were prepared using the double desolvation technique and were characterized in vitro, ex vivo and in vivo. Results of the ex vivo cellular uptake study indicated 5--fold higher uptake of didanosine from the mannan-coated nanoparticles formulation (62.5 ± 5.4%) by the macrophages in comparison with didanosine solution in phosphate buffer saline (PBS, pH 7.4) (12.1 ± 2.3%). The better cellular uptake from the nanoparticles formulation was further confirmed by fluorescence microscopy using hydrophilic 6-carboxyfluorescein as a marker. Results of the quantitative biodistribution study showed 1.7, 12.6 and 12.4 times higher localization of didanosine in the spleen, lymph nodes and brain, respectively, after administration of mannan-coated nanoparticles compared to that after injection of didanosine solution in PBS (pH 7.4). Results of the present study showed that the mannan-coated nanoparticles targeted didanosine to the macrophage by mannosyl receptor mediated endocytosis.