Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.ejpb.2011.10.014
Title: Loading 3-deazaneplanocin A into pegylated unilamellar liposomes by forming transient phenylboronic acid-drug complex and its pharmacokinetic features in Sprague-Dawley rats
Authors: Sun, F. 
Li, J.
Yu, Q.
Chan, E. 
Keywords: 3-Deazaneplanocin A
Epigenetic anticancer agent
Nucleoside analogs
Pegylated liposomes
Pharmacokinetics
Phenylboronic acid
Issue Date: Feb-2012
Citation: Sun, F., Li, J., Yu, Q., Chan, E. (2012-02). Loading 3-deazaneplanocin A into pegylated unilamellar liposomes by forming transient phenylboronic acid-drug complex and its pharmacokinetic features in Sprague-Dawley rats. European Journal of Pharmaceutics and Biopharmaceutics 80 (2) : 323-331. ScholarBank@NUS Repository. https://doi.org/10.1016/j.ejpb.2011.10.014
Abstract: 3-Deazaneplanocin A (DZNep) is an attractive epigenetic anticancer agent through the inhibition of the cellular enhancer of zeste homolog 2 (EZH2) protein. The purpose of this study was to improve the pharmacokinetic characteristics of DZNep in vivo through developing a unilamellar pegylated liposomal formulation encapsulating DZNep (L-DZNep). A remote-loading method in the presence of phenylboronic acid (R-w-PBA) was developed to stably encapsulating DZNep inside liposomes (encapsulation efficiency = 50.7% at molar ratio of 1:10 of drug to lipids) through forming a transient PBA-DZNep complex. The pharmacokinetics of L-DZNep was investigated in Sprague-Dawley rats. In comparison with free drug, encapsulation of the DZNep in pegylated liposomes resulted in 99.3% reduction of the plasma clearance, whereas it increased the elimination half-life from 1.1 h to 8.0 h and the area under the plasma concentration curve by 138-fold. These findings demonstrate a novel approach (R-w-PBA method) through the development of L-DZNep, which may be extensively applied for the encapsulation of hydrophilic nucleoside analogs containing vicinal hydroxyl groups and protonable amino in the pegylated liposomes. Additionally, the pegylated liposomes could effectively prolong the retention of DZNep in the systemic circulation and therefore is highly likely to increase the DZNep's tumor localization. © 2011 Elsevier B.V. All rights reserved.
Source Title: European Journal of Pharmaceutics and Biopharmaceutics
URI: http://scholarbank.nus.edu.sg/handle/10635/109758
ISSN: 09396411
DOI: 10.1016/j.ejpb.2011.10.014
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