期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 100, 期 6, 页码 2311-2320出版社
ELSEVIER SCIENCE INC
DOI: 10.1002/jps.22469
关键词
dendrimers; methotrexate; lactoferrin; lung targeting; nanoconstructs; pulmonary drug delivery; cancer chemotherapy; drug targeting; macromolecular drug delivery
资金
- All India Council of Technical Education, New Delhi, India
The present investigation was aimed at developing and exploring the potential of lactoferrin (Lf)-conjugated dendritic nanocomposite for lung targeting of methotrexate (MTX). The 5.0G poly(propylene imine) (PPI) dendrimer and Lf-conjugated 5.0G 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 5.0G PPI dendrimer-based formulations to be approximately 1.5 times and 2.5 times superior to plain 5.0G PPI dendrimer as well as pure MTX, respectively, for lung targeting of anticancer drugs. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:2311-2320, 2011
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