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 great potential for use in drug delivery. However, a primary complication of this research stems from the prevalence of 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 a poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA) homopolymer and a non-degradable ethylene glycol dimethacrylate or acid-labile diacetal-based bis[(2-methacryloyloxy)ethoxymethyl] ether cross-linker. Subsequently, OEGMA addition resulted in the 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 under 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.