Background: Despite the advancement in the development of newer anti-HIV
drugs, various drawbacks still persist with antiretroviral therapy. Therefore, this study
was conducted to overcome the pharmacokinetic limitations of commonly prescribed
anti-HIV drugs with the implication of nanotechnology.
• Formulation of nanoparticles carrying antiretroviral drugs.
• Pharmacokinetic and pharmacodynamic study of nanoparticles loaded with antiretroviral
drugs viz zidovudine (AZT), didanosine (ddI), and ritonavir (RTV).
• Ex vivo study of nanoparticles loaded with antiretroviral drugs.
Methods: Poly (lactide-co-glycolide) (PLGA) nanoparticles encapsulating AZT, ddI and
RTV were developed by multiple emulsion solvent evaporation technique and characterized
for size, shape, zeta potential, polymer drug interaction etc. Comparative pharmacokinetic
studies were carried out following single oral dose administration of free or
nano drugs in mice.
Results: PLGA nanoparticles loaded with HIV drugs were found to be stable and in nanorange.
FTIR images of ddI and RTV did not show any interaction of these drugs with
polymer except for AZT. The absence of any sharp diffraction peaks in the XRD of encapsulated
drugs indicated complete amorphization of drugs in nanoparticles. The pharmacokinetic
parameters were significantly improved upon nanoencapsulation as compared
to the parent drugs. Fluorescent nanoparticles were found to be efficiently taken up
by peritoneal macrophages and cytotoxicity assay indicated that PLGA nanoparticles are
safe to be used as drug delivery system.
Conclusion: PLGA nanoparticles exhibited sustained release of AZT, ddI and RTV in
mice with improved pharmacokinetic parameters and hold great prospective for extended
research in higher animals.