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Poly(D,L-lactic-co-glycolic acid) (PLGA) is the most frequently used bioresorbable polymer for the controlled release of drugs. Hydrophilic additives such as poly(ethylene glycol) (PEG) are commonly incorporated into PLGA to enhance the release of hydrophobic drugs such as paclitaxel (PCTX). Understanding the factors and mechanisms that govern drug release in a blended system is important to be able to modify the delivery properties of the drugs. This study evaluated the mechanical properties of PCTX-eluting PLGA thin films that incorporate PEG additives under constant hydration, which mimics physiological conditions. The presence of additives resulted in varying extents of phase separation, which changed the degradation and release profiles of the PLGA films. The incorporation of long-chain additives resulted in large phase-separated additive-rich domains that gave rise to large pores, high mass loss, and a high burst release of PCTX from the extensive dissolution and leaching of additives upon hydration. Subsequently, the degradation rate of PLGA films was reduced by the out-diffusion of acidic byproducts through these water-filled pores and channels; these byproducts would otherwise accumulate and contribute to higher degradation rates due to the autocatalysis of PLGA. The preferential association between PCTX and PEG additives in the phase-separated PLGA films was exploited to enhance the release of hydrophobic PCTX, and statistical correlations were established between the simultaneous release of PCTX and additives. This significant correlation could provide useful information for the prediction of hydrophobic drug release profiles and the selection or preparation of localized drug delivery systems with the use of PEG additives. Bioresorbable materials are crucial for medical and pharmaceutical applications such as implants and drug delivery. They can host drug molecules, carry them in the body, and release them over a period of time through diffusion or degradation of the material. A biodegradable and biocompatible polymer known as poly(lactic-co-glycolic acid) (PLGA) has proved particularly attractive. PLGA's slow release of hydrophobic drugs, a potential obstacle to drug delivery, can be addressed through the incorporation of hydrophilic additives such as polyethylene glycol (PEG). Joachim Loo from Nanyang Technological University and co-workers have now determined the precise influence of PEG — the length of the molecules and their concentration — on the mechanical properties, and thus the degradation, of PLGA thin films containing a hydrophobic chemotherapeutic drug, paclitaxel. The system was constantly kept in aqueous conditions to mimic physiological conditions. Insights gained into the degradation mechanism leading to the release of paclitaxel will inform the development of localized drug delivery systems. The influence of hydrophilic additives on the underlying factors and mechanisms that govern the release of the hydrophobic drug PCTX from a blended system was investigated. The incorporation of hydrophilic PEG additives resulted in a phase-separated system with randomly distributed PCTX–PEG-rich domains in the continuous PLGA matrix. Owing to their preferential association in these domains, the enhanced release of PCTX can be controlled and modulated by varying the concentration and MW of PEG additives. The extensive porosity due to the dissolution of PCTX–PEG domains created a significant reduction in the tensile strength of these films as evaluated under constant aqueous conditions.