Tunable Degradation of Copolymers Prepared by Nitroxide-Mediated Radical Ring-Opening Polymerization and Point-by-Point Comparison with Traditional Polyesters

Abstract

Two libraries of well-defined, degradable vinyl copolymers of opposite solubility, based either on methyl methacrylate (MMA) or on oligo(ethylene glycol) methyl ether methacrylate (OEGMA), and containing various amount of 2-methylene-4-phenyl-1,3-dioxolane (MPDL), were synthesized by nitroxide-mediated radical ring-opening polymerization. A comprehensive degradation study (long-term hydrolytic degradation, degradation of thick and thin films, water uptake, enzymatic degradation) was then performed and results were compared with those from traditional aliphatic polyesters (PLGA, PLA and PCL). It appeared that P(MMA-co-MPDL) copolymers slowly degraded in PBS with degradation kinetics slower than that of PCL whereas P(OEGMA-co-MPDL) copolymers led to significant degradation, in between that of PLA and PCL, depending on the amount of MPDL, but without leading to a dramatic drop of pH as for PLGA and PLA. Whereas P(MMA-co-MPDL) copolymers might be well-suited for biomaterials intended for long-term use (e.g., devices, implants), faster degrading P(OEGMA-co-MPDL) copolymers might be envisioned for short-or mid-term applications such as nanoscale drug-delivery systems and meet a need for hydrophilic degradable materials with tunable degradation kinetics.

Degradable polymer prodrugs with adjustable activity from drug-initiated radical ring-opening copolymerization

“…We can hypothesize for P(MMA- co -MPDL) nanoparticles that only the surface fraction of Gem is released whereas the fraction which is buried into the nanoparticle's core will be accessible and released only when the nanoparticles are degraded. 66 As for soluble P(OEGMA- co -MPDL) prodrugs, which are essentially molecularly dissolved even for the highest amounts of MPDL (Fig. S18 † ), they will form a protective P(OEGMA- co -MPDL) shroud wrapped around the drug, efficiently protecting the drug-linker moiety from enzymes, similarly to what is observed with PEGylated peptides/proteins.…”

Degradable Copolymer Nanoparticles from Radical Ring-Opening Copolymerization between Cyclic Ketene Acetals and Vinyl Ethers

“…copolymers. 48 Also, P(MEO 2 MA-co-OEGMA-co-BMDO) terpolymers subjected to identical degradation conditions were not entirely degraded after 24 h (only ~40% of the main-chain ester groups were hydrolysed). 19 Similarly, copolymers based on MDO and PEGMA (F MDO = 0.5) incubated in the presence of lipase from Pseudomonas cepacia led to uncompleted degradation (not quantified) even after 5 days at 37 °C.…”

Radical Ring-Opening Copolymerization-Induced Self-Assembly (rROPISA)

“…33,34 Recent years have seen a resurgence of interest in CKAs, which may be explained, at least in part, by their ability to copolymerize with traditional vinyl monomers (e.g., vinyl acetate, methacrylic esters) by both conventional free-radical polymerization and RDRP techniques. [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] However, to the best of our knowledge, there is no example of PISA systems or emulsion/dispersion (co)polymerizations based on CKAs. Only two related studies have been published so far.…”