Synthesis and Evaluation of Boronated 4‐Arm Polyethylene Glycol for Application in Transmucosal Drug Delivery

Abstract

AbstractPolyethylene glycol (PEG) exhibits poor residence on mucosal membranes in the presence of biological fluid, and the influence of PEG boronation on its properties has never been investigated. This project aimed to synthesise boronated 4‐arm PEG and evaluate their pH stability, thermal properties and mucoadhesiveness for potential transmucosal applications. Two types of boronated 4‐armed PEG (B4PEG1 & B4PEG2) and a boronated linear PEG (BLPEG) were synthesized. The degree of boronation, mucoadhesiveness, thermal and pH stability of the polymers were assessed using 1H NMR spectroscopy, viscometry, thermogravimetric analysis and UV–visible spectroscopy, respectively. Gel Permeation Chromatography was employed to confirm PEG boronation. The respective degrees of boronation for B4PEG1 and B4PEG2 were 32.8 % and 46.2 %. The molecular architecture and degree of PEG boronation had a remarkable influence on mucoadhesiveness, pH, and thermal stability. B4PEG2, with a branched architecture and the greatest degree of boronation, exhibited superior mucoadhesiveness and colloidal stability at pH 4 to 8, relative to B4PEG1 and BLPEG. Boronation improved the thermal stability of 4‐arm PEG. This study is the first to demonstrate that PEG boronation could enhance the pH‐sensitivity, thermal stability and mucoadhesiveness of 4‐arm PEG. Boronated 4‐arm PEGs could serve as mucoadhesive polymeric excipients for transmucosal drug delivery.