Exploring structure and dynamics of the polylactic-co-glycolic acid-polyethylene glycol copolymer and its homopolymer constituents in various solvents using all-atom molecular dynamics

Polylactic-co-glycolic acid (PLGA)-basedpolymers are synthetic materials that are prominent in drug delivery. PLGA homopolymer is biodegradable, biocompatible and is often polymerized to polyethylene glycol (PEG) to form a block copolymer used to form core-shell nanoparticles. PEG is known for reducing blood clearance and opsonization, in addition to imparting "stealth" properties to various drugs and biomaterials. Current formulation methodologies for PLGA-PEG copolymer nanoparticles can be tuned to control key parameters for improved therapeutic delivery; however, molecular-level understanding of copolymersolvent interactions during nanoparticle formulation is lacking. Therefore, three different PLGA-PEG/solvent pairs are examined, in comparison to their homopolymer constituents, to better understand copolymerization effects and its impact on nanoparticle formulation. Results show that at room temperature PLGA-PEG oligomers in dimethyl sulfoxide are the most rigid in good solvent conditions (Flory exponent >0.5) and have the largest end-to-end relaxation times when compared to acetone and water. PEG has a Flory exponent of similar to 0.5 in both water and acetone, showing that the molecular dynamic model that is employed can reproduce its amphiphilic nature in solution. Knowledge of PLGA-PEG structure and dynamics can be used in the design of novel biomedical technologies that improve drug efficacy and reduce cost of treatment.