alexa Synthesis, characterization and targeting potential of zidovudine loaded sialic acid conjugated-mannosylated poly(propyleneimine) dendrimers.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Bioequivalence & Bioavailability

Author(s): Gajbhiye V, Ganesh N, Barve J, Jain NK

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Abstract The present investigation was aimed at exploring dual targeting of anti-HIV drug, zidovudine (ZDV) via sialic acid conjugated-mannosylated poly(propyleneimine) (PPI) dendritic nano-constructs. Fourth generation PPI dendrimers, sialic acid conjugated PPI dendrimers (SPPI), mannose conjugated PPI dendrimers (MPPI) and dual ligand system i.e. sialic acid conjugated-mannosylated PPI dendrimers (SMPPI) were synthesized and characterized by FT-IR and (1)H NMR spectroscopies and were further confirmed by size exclusion chromatography and differential scanning calorimetry. Various parameters like drug loading, pH dependent in vitro release, hemolytic toxicity, macrophage uptake and cytotoxicity concerning PPI, SPPI, MPPI and SMPPI dendrimers were evaluated. ZDV loaded SMPPI, SPPI and MPPI have shown reduced hemolytic toxicity, cytotoxicity and in vitro drug release at pH 7.4. Extremely significant (P<0.001) increase in cellular uptake of ZDV by macrophage cells was observed in case of SMPPI as compared to PPI and free drug. The in vivo blood level and tissue distribution studies in albino rats also demonstrated potential of dual targeted system towards sialoadhesin and carbohydrate receptors. The drug concentration in lymph nodes was increased to about 28 times in case of SMPPI (1335 ± 17.6 ng/g) as compared to free drug (48 ± 5.8 ng/g) at 6th hr. The results suggested that such dual ligand dendritic system (SMPPI) hold potential to enhance biocompatibility and site specific delivery of antiretroviral drug, ZDV. Copyright © 2013 Elsevier B.V. All rights reserved. This article was published in Eur J Pharm Sci and referenced in Journal of Bioequivalence & Bioavailability

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