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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 copolymer‐solvent 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 ~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.

Titania (TiO₂) is used extensively in biomedical applications; efforts to boost the biocompatibility of TiO₂include coating it with the titania binding hexamer, RKLPDA. To understand the binding mechanism of this peptide, we employ molecular dynamics simulations enhanced by metadynamics to study three amino acids present in the peptide—arginine (R), lysine (K), and aspartate (D), on four TiO₂variants that have different degrees of surface hydroxyl groups. We find that binding is a function of both sidechain charge and structure, with R binding to all four surfaces, whereas the affinity of K and D is dependent on the distribution of hydroxyl groups. Informed by this, we study the binding of the titania binding hexamer and dodecamer (RKLPDAPGMHTW) on two of the four surfaces, and we see strong correlations between the binding free energy and the primary binding residues, in agreement with prior experiments and simulations. We propose that the discrepancies observed in prior work stem from distribution of surface hydroxyl groups that may be difficult to precisely control on the TiO₂interface.