Acta Pharm. 58 (2008) 61-74
Original research paper
Mannan-coated gelatin
nanoparticles for sustained and targeted delivery of didanosine: In vitro and in vivo evaluation
AMANDEEP
KAUR, SUBHEET JAIN and ASHOK K. TIWARY
subheetjain@rediffmail.com
Department of Pharmaceutical Sciences and Drug
Research,
Accepted February 5, 2008
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.
Keywords: macrophage,
targeting, didanosine, anti-HIV, mannan, receptor mediated endocytosis