Glucose-Responsive Gene Delivery at Physiological pH through Tertiary-Amine Stabilized Boronate-PVA Particles Synthesized by One-Pot Reaction

• Published in: Pharmaceutics 2021-01, Vol.13 (1), p.62
• Main Authors: Morey, Mangesh, Srivastava, Akshay, Pandit, Abhay
• Format: Article
• Language: English
• Subjects: Acids; boronic acid; drug delivery; Enzymes; free radical polymerization; Glucose; glucose-responsive gene delivery; NMR; Nuclear magnetic resonance; Physiology; Polymerization; Polyvinyl alcohol; Scanning electron microscopy
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics13010062

We report a physiologically stable and cytocompatible glucose-responsive nonviral gene delivery system made up of boronate functionalized polymeric material. Herein, we utilize boronate -diol interactions to develop a glucose-responsive submicron particle (SMP) system. The stability of the boronate interaction at a physiological pH was achieved by copolymerization of dimethyl aminoethyl methacrylate (DMAEMA) with acrylamidophenylboronic acid (AAPBA) and the formation of a complex with polyvinylalcohol (PVA) which is governed by -diol interactions. The shift in hydrodynamic diameter of SMPs was observed and correlated with increasing glucose concentrations at a physiological pH. Optimal transfection was observed for a 5 µg dose of the gaussia luciferase reporter gene in NIH3T3 cells without any adverse effect on cellular viability. The destabilization of the AAPBA-PVA complex by interacting with glucose allowed the release of encapsulated bovine serum albumin (BSA) in a glucose-responsive manner. In total, 95% of BSA was released from SMPs at a 50 mM glucose concentration after 72 h. A two-fold increase in transfection was observed in 50 mM glucose compared to that of 10 mM glucose.