Although further improvements in terms of model accuracy could be implemented, this work demonstrates that thermodynamic quantities estimated via MD simulations can help to anticipate drug release kinetics from PLGA matrices. In addition, this study provides evidence of molecular partitioning, especially in the case of PEG-DTXL conjugates, at the matrix-water interface. The proposed approach could be used to predict the pharmacological behavior of PLGA implants loaded with a variety of payloads under different conditions.