In recent decades, polymer based delivery platforms have attracted increasing attention due to the ability to release therapeutics at a controlled rate. The release profile can be customized in terms of quantity of drug released and release time depending on the therapeutic application. However, experimental optimization of drug release kinetics requires intensive, time-consuming and costly optimization steps. Molecular Dynamics simulations can be used as a predictive tool to reduce the experimental workload. Coarse-grained models and enhanced sampling approaches can be combined to describe or phenomenologically explain drug release kinetics that occur at large spatial and temporal scales not easily accessible by atomistic simulations and unbiased approaches. Among polymer candidates, the FDA approved Poly-lactic-glycolic-acid (PLGA) is a biodegradable and safe polymer largely used for the manufacture of delivery systems. It has been used to release small molecules and biologicals mostly against cancer and cardiovascular diseases, and in implantable devices, for the long-term and sustained release of therapeutic molecules to modulate inflammation and tissue regeneration. Typically, drug release kinetics will depend on drug-related parameters such as solubility, size, and shape as well as carrier-related factors such as composition, shape, size, and stiffness -the higher the drug retention within the carrier, the slower the drug release rate. The prodrug design, in which the drug is covalently conjugated to a moiety, has proven to be a valuable strategy for adjusting the solubility, shape and size of the therapeutic agent toward improving the drug retention. Furthermore, when exposed to the particle surface, the conjugated moiety can bind a receptor and thus mediate the anchoring of the drug or particle to a biological target. Also, in response to environmental stimuli, it can become susceptible to cleavage so to facilitate the release of the drug in its active configuration in a desired site. The impact of the mechanical and physicochemical properties of PLGA-based materials on drug release kinetics have been extensively studied and characterized experimentally. After fabrication, the drug trapped in the amorphous PLGA matrix is poorly mobile. Upon suspension of the particle in an aqueous solvent, water permeates the particle and acts as a plasticizer. As a consequence, the mechanical and physicochemical properties of the polymer matrix will change, as will do the transport properties. The PLGA polymer begins to degrade due to the hydrolytic cleavage of its polyester backbone, becoming more and more hydrophilic as it shortens. In this phase, the translocation of the drug from the polymer matrix into the aqueous solvent intertwines with the simultaneous efflux of polymer fragments. Despite the extensive use of PLGA in biomedical applications, in-silico investigations remain limited due to the lack of a PLGA model suitable to investigate large-scale phenomena. We have recently developed and validated an atomistic model for PLGA relying on the 2016H66 force field to investigate the physicochemical and mechanical properties of a pure PLGA matrix and PLGA/ polyethylene glycol (PEG) mixtures. In this study, molecular models of PLGA, free docetaxel (DTXL) and DTXL conjugated to moieties of varying solubility and size are constructed at coarse-grained (CG) resolution for computational efficiency, employing the MARTINI force field (version 2.2) as to preserve chemical diversity. The CG PLGA model is validated for the reproducibility of the polymer matrix properties computed at atomistic resolution relevant for the release of encapsulated compounds into the aqueous solution.