Acid-labile and non-degradable cross-linked star polymer model networks by aqueous polymerization for in situ encapsulation and release

Biocompatible, acid-labile cross-linked star polymer model networks (CSPMNs) have a great potential for use in drug delivery. However, a primary complication of this research stems from the prevalence for their synthesis to take place in organic solvents. Herein, to minimize CSPMN potential cytotoxicity, aqueous reversible addition-fragmentation chain transfer polymerization is employed for their synthesis. Initially, “arm-first” star polymers were synthesized in water using poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA) homopolymer and, non-degradable ethylene glycol dimethacrylate or acid-labile diacetal-based bis[(2-methacryloyloxy)ethoxymethyl] ether cross-linker. Subsequently, OEGMA addition resulted in preparation of “in-out” star polymers (with higher molecular weights) followed by cross-linker addition to form CSPMNs. Rhodamine B dye encapsulation was performed during CSPMN synthesis and its release was observed in biologically relevant conditions. Having shown the effective breakdown of the diacetal-based CSPMNs, their potential for use in drug delivery in low pH environments (i.e. cancerous tumors) is expected to be high.