A Coarse-Grained Molecular Dynamics Description of Docetaxel-Conjugate Release from PLGA Matrices

[Image: see text] Despite the extensive use of poly-lactic-glycolic-acid (PLGA) in biomedical applications, computational research on the mesoscopic characterization of PLGA-based delivery systems is limited. In this study, a computational model for PLGA is proposed, developed, and validated for the reproducibility of transport properties that can influence drug release, the rate of which remains difficult to control. For computational efficiency, coarse-grained (CG) models of the molecular components under consideration were built using the MARTINI force field version 2.2. The translocation free energy barrier ΔG(t)(*) across the PLGA matrix in the aqueous phase of docetaxel and derivatives of varying sizes and solubilities was predicted via molecular dynamics (MD) simulations and compared with experimental release data. The thermodynamic quantity ΔG(t)(*) anticipates and can help explain the release kinetics of hydrophobic compounds from the PLGA matrix, albeit within the limit of a drug concentration below a critical aggregation concentration. The proposed computational framework would allow one to predict the pharmacological behavior of polymeric implants loaded with a variety of payloads under different conditions, limiting the experimental workload and associated costs.