alexa Lactoferrin-conjugated dendritic nanoconstructs for lung targeting of methotrexate.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Bioequivalence & Bioavailability

Author(s): Kurmi BD, Gajbhiye V, Kayat J, Jain NK

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Abstract The present investigation was aimed at developing and exploring the potential of lactoferrin (Lf)-conjugated dendritic nanocomposite for lung targeting of methotrexate (MTX). The 5.0 G poly(propylene imine) (PPI) dendrimer and Lf-conjugated 5.0 G PPI dendrimer were synthesized and characterized by Fourier-transform infrared spectroscopy, nuclear magnetic resonance, and transmission electron microscopy. The entrapment efficiency, in vitro release, and hemolytic toxicity were assessed. Pharmacokinetic and organ distribution studies were carried out to evaluate in vivo targeting potential of developed system. The pharmacokinetic studies showed that elimination half-life of MTX-loaded plain PPI dendrimer (10.41 ± 2.12 h, p < 0.05) and MTX-loaded Lf-conjugated PPI dendrimer (12.23 ± 1.53 h, p < 0.01) was significantly higher than the free drug (5.85 ± 1.19 h). Organ distribution assessment of different formulations displayed significant (p <0.05) higher accumulation of drug in lungs by MTX-Lf-PPI (1329 ± 26.7 ng/g of tissue) as compared with MTX-PPI (721 ± 23.4 ng/g of tissue) and free MTX (575 ± 19.7 ng/g of tissue) after 6 h of administration. The result suggested that Lf-conjugated 5.0 G PPI dendrimer-based formulations to be approximately 1.5 times and 2.5 times superior to plain 5.0 G PPI dendrimer as well as pure MTX, respectively, for lung targeting of anticancer drugs. Copyright © 2011 Wiley-Liss, Inc. This article was published in J Pharm Sci and referenced in Journal of Bioequivalence & Bioavailability

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