Abbas Hemati Azandaryani1,2, Soheila Kashanian3,4, Mohsen Shahlaei1, Katayoun Derakhshandeh5, Marjan Motiei6, Sajad Moradi1. 1. Nano Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran. 2. Department of Applied Chemistry, Faculty of Chemistry, Razi University, Kermanshah, 6714967346, Iran. 3. Nano Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran. Kashanian_s@yahoo.com. 4. Department of Applied Chemistry, Faculty of Chemistry, Razi University, Kermanshah, 6714967346, Iran. Kashanian_s@yahoo.com. 5. Department of Pharmaceutics, Faculty of Pharmacy, Hamedan University of Medical Sciences, Hamedan, 6517838678, Iran. 6. Centre of Polymer Systems, Tomas Bata University in Zlin, Tr. Tomase Bati 5678, 760 01, Zlín, Czech Republic.
Abstract
PURPOSE: The aim of this study is to show a new mesomicroscopic insight into Letrozole (LTZ) loaded nanocomplexes and their ex vivo characteristics as a drug delivery system. METHODS: The LTZ loaded hybrid chitosan-based carrier was fabricated using a modified ionic crosslinking technique and characterized in more detail. To understand the mechanism of LTZ action encapsulated in the hybrid polymer-lipid carrier, all-atom molecular dynamics simulations were also used. RESULTS: The physicochemical properties of the carrier demonstrated the uniform morphology, but different drug loading ratios. In vitro cytotoxic activity of the optimized carrier demonstrated IC50 of 67.85 ± 0.55 nM against breast cancer cell line. The ex vivo study showed the positive effect of nanocomplex on LTZ permeability 7-10 fold greater than the free drug. The molecular dynamic study also confirmed the prsence of hydrophobic peak of lipids at a distance of 5 Å from the center of mass of LTZ which proved drug entrapment in the core of nanocomplex. CONCLUSIONS: The hybrid nanoparticle increased the cytotoxicity and tissue permeability of LTZ for oral delivery. This study also confirmed the atomic mesostructures and interaction of LTZ in the core of hybrid polymer-lipid nanoparticles.
PURPOSE: The aim of this study is to show a new mesomicroscopic insight into Letrozole (LTZ) loaded nanocomplexes and their ex vivo characteristics as a drug delivery system. METHODS: The LTZ loaded hybrid chitosan-based carrier was fabricated using a modified ionic crosslinking technique and characterized in more detail. To understand the mechanism of LTZ action encapsulated in the hybrid polymer-lipid carrier, all-atom molecular dynamics simulations were also used. RESULTS: The physicochemical properties of the carrier demonstrated the uniform morphology, but different drug loading ratios. In vitro cytotoxic activity of the optimized carrier demonstrated IC50 of 67.85 ± 0.55 nM against breast cancer cell line. The ex vivo study showed the positive effect of nanocomplex on LTZ permeability 7-10 fold greater than the free drug. The molecular dynamic study also confirmed the prsence of hydrophobic peak of lipids at a distance of 5 Å from the center of mass of LTZ which proved drug entrapment in the core of nanocomplex. CONCLUSIONS: The hybrid nanoparticle increased the cytotoxicity and tissue permeability of LTZ for oral delivery. This study also confirmed the atomic mesostructures and interaction of LTZ in the core of hybrid polymer-lipid nanoparticles.
Authors: Yunsheng Xia; Trung Dac Nguyen; Ming Yang; Byeongdu Lee; Aaron Santos; Paul Podsiadlo; Zhiyong Tang; Sharon C Glotzer; Nicholas A Kotov Journal: Nat Nanotechnol Date: 2011-08-21 Impact factor: 39.213