for the Na-Na dimer model, considering also that the chain and the solvent are both made by Na type beads. This unexpected, suboptimal solubility of PLGA in acetone at the CG level (𝜐 =0.44 ± 0.01), conversely to the atomistic case (𝜐 = 0.58 ± 0.003), must be attributed to the slight interpenetration of adjacent beads, as described above, that would cause a partial collapse of the chain. The discrepancies between the values estimated at atomistic and coarse-grained levels are narrow for PLGA chains modeled with a dimeric P1-C5 unit (Figure ), as compared to the alternative Na-Na and Na-N0 cases (Figures and). The more hydrophilic P1 beads, as compared to the Na type beads, likely contributed to reduce the artificial intrachain higher affinity and the partial collapse of the chain. Finally, the miscibility of PLGA and PEG was also estimated at CG level and compared with the atomistic results. First, the three alternative mapping schemes for PLGA were tested to check for the The normalized number of interspecies contacts along 1 µs for the 4 configurations, as previously computed from atomistic simulations , was accurately reproduced at the CG level by the Na-Na mapping scheme (Figure ): at a lower PEG concentration, PLGA blends well with both shorter PEG16 and longer PEG64 chains (systems A and B), the miscibility partially reduces at higher concentration of shorter PEG16 chains (systems C), and segregation occurs in the system with the higher concentration of longer PEG64 chains (systems D). Visual evidence of the four PLGA/PEG miscibility regimes as a function of polymers ratio (ΦPEG=8%, 46%) and length (NPEG=16, 64) is reported in Figure . The miscibility regimes previously characterized at the atomistic level are instead poorly reproduced when using the alternative dimeric P1-C5, Na-N0 and (S)Na-Na configurations (Figure ). In the case of the combination (S)Na-Na, the PLGA-PEG miscibility trend was not reproduced as a likely consequence of the recently emerged undesired effects rising when mixing particles of different sizes described elsewhere. 28 Based on the results discussed above, for the release studies below we chose to represent PLGA using the Na-Na mapping scheme, which reasonably reproduced properties of interest for this work.