The interface between solid poly(lactic acid-co-glycolic acid), PLGA, and solvents is described by large-scale atomistic simulations for water, ethyl acetate, and the mixture of them at ambient conditions. Interactions at the interface are dominated by Coulomb forces for water and become overwhelmingly dispersive for the other two solvents. This effect drives a neat liquid-phase separation of the mixed solvent, with ethyl acetate covering the PLGA surface and water being segregated away from it. We explore with all-atom Molecular Dynamics the formation of macromolecular assemblies on the surface of the PLGA-solvent interface when DSPE-PEG, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(polyethylene glycol)n amine, is added to the solvent. By following in time the deposition of the DSPE-PEG macromolecules onto the PLGA surface, the mechanism of how nanopatches remain adsorbed to the surface despite the presence of the solvent is probed. These patches have a droplet-like aspect when formed at the PLGA-water interface that flatten in the PLGA-ethyl acetate interface case. Dispersive forces are dominant for the nanopatch adhesion to the surface, while electrostatic forces are dominant for keeping the solvent around the new formations. Considering the droplet-like patches as wetting the PLGA surface, we predict an effective wetting behavior at the water interface that fades significantly at the ethyl acetate interface. The predicted mechanism of PEG-lipid nanopatch formation may be generally applicable for tailoring the synthesis of asymmetric PLGA nanoparticles for specific drug delivery conditions.