Investigation of morphologies and structures of drug and PEG-b-PLA diblocks by dissipative particle dynamics simulations

Abstract Polymeric drug carriers have conventionally been recognized for their significance in augmenting drug stability and solubility. Poly(lactide) (PLA) and poly(ethylene glycol) (PEG) are two polymers that have received considerable attention in this context. However, a comprehensive exploration of the factors that impact the final morphology and structure of both PEG- b -PLA copolymer and drug has yet to be undertaken. In this study, we present findings from a comprehensive investigation into the self-assembly behavior of PEG- b -PLA copolymers and model drug in aqueous environments, utilizing dissipative particle dynamics simulations. Our simulations show that drug and PEG- b -PLA could self-assemble into core–shell spherical micelles. The spherical micelles are comprised of the drug hydrophobic core, the PLA hydrophobic middle layer, and the PEG hydrophilic shell. As the PEG 5 - b -PLA 10 concentration increases, the drug-loaded PEG- b -PLA system undergoes a structural evolution from spherical micelles to cylindrical micelles, ultimately forming perforated layered structures. Additionally, their self-assembly morphologies can also be regulated by the PEG-b-PLA copolymer compositions. Specifically, and PEG 5 - b -PLA 10 , PEG 5 - b -PLA 15 , PEG 5 - b -PLA 20 copolymers demonstrate the ability to form well-organized core–shell configurations. PEG 5 - b -PLA 10 exhibits a drug load of 0.08, which is better suited for drug loading, in comparison with the PEG 5 - b -PLA 15 and PEG 5 - b -PLA 20 systems. For PEG 5 - b -PLA 10 system, the simulation results show that the suitable concentration of PEG 5 - b -PLA 10 copolymer is 10%–15%. The higher molecular weight copolymer exhibits slower drug release kinetics under shear flow. These simulation results offer novel insights into the self-assembly process of drug and PEG- b -PLA diblocks, elucidating the underlying physical mechanisms at the molecular level.