Influence of PEG chain length on colloidal stability of mPEGylated polycation based coacersomes for therapeutic protein delivery

Abstract

The polycation/polyanion based coacervate platform for therapeutic protein delivery finds difficulty in their colloidal stability under physiological environment. To overcome this issue, PEGylation could be a versatile strategy to enhance colloidal stability. Herein, a poly(ethylene arginyl aspartate diglyceride) (PEAD) polycation was synthesized, and a series of methoxy polyethylene glycols (mPEG) including mPEG350, mPEG750 and mPEG2000 were attached with PEAD polycation to obtain mPEG350-PEAD, mPEG750-PEAD and mPEG2000-PEAD respectively. The PEAD and mPEGylated PEADs were complexed with heparin (HEP) to fabricate coacervate (Coa) and coacersome (mP_Coa) particles respectively. The colloidal stability of Coa and mP_Coa coacersomes has been investigated by dynamic light scattering (DLS) and microscopic techniques. The vascular endothelial growth factor 165 (VEGF-165) was encapsulated in the Coa or mP_Coa particles and administered to human umbilical vein endothelial cells (HUVECs) to induce a tubular network formation in vitro. All the polycations are highly biocompatible and exhibit more than 94 % of VEGF-165 loading efficiency. An effect of mPEG chain length on colloidal stability of mP_Coa and in vitro tubular formation ability of HUVECs has been investigated. (C) 2019 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.