a coarse-grained molecular dynamics description of docetaxel-conjugate release from plga matrices

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 models of the molecular components under consideration are 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 size and solubility is predicted via Molecular Dynamics simulations and compared with the experimental release data. The thermodynamic quantity 〖ΔG〗_t^* anticipate, if predicted via simulations, and can help to explain the release kinetics of hydrophobic compounds from the PLGA matrix, albeit within the limit of a drug concentration below a critical aggregation concentration. In addition, this study provides a viable approach for optimizing the particle coating with ligands having desired orientation and stability.