Loading 3-deazaneplanocin A into pegylated unilamellar liposomes by forming transient phenylboronic acid-drug complex and its pharmacokinetic features in Sprague-Dawley rats.

摘要: Abstract 3-Deazaneplanocin A (DZNep) is an attractive epigenetic anticancer agent through the inhibition of cellular enhancer zeste homolog 2 (EZH2) protein. The purpose this study was to improve pharmacokinetic characteristics DZNep in vivo developing a unilamellar pegylated liposomal formulation encapsulating (L-DZNep). remote-loading method presence phenylboronic acid (R-w-PBA) developed stably inside liposomes (encapsulation efficiency = 50.7% at molar ratio 1:10 drug lipids) forming transient PBA–DZNep complex. pharmacokinetics L-DZNep investigated Sprague–Dawley rats. In comparison with free drug, encapsulation resulted 99.3% reduction plasma clearance, whereas it increased elimination half-life from 1.1 h 8.0 h and area under concentration curve by 138-fold. These findings demonstrate novel approach (R-w-PBA method) development L-DZNep, which may be extensively applied for hydrophilic nucleoside analogs containing vicinal hydroxyl groups protonable amino liposomes. Additionally, could effectively prolong retention systemic circulation therefore highly likely increase DZNep’s tumor localization.