Investigation of morphologies and structures of Phloretin drug and PEG-b-PLA diblocks: A Dissipative particle dynamics simulations study 

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 phloretin drug has yet to be undertaken. In this study, we present findings from a comprehensive investigation into the self-assembly behavior of PEG-PLA copolymers and Phloretin drug in aqueous environments, utilizing DPD simulations. Our simulations show that phloretin drug and PEG-b-PLA could self-assemble into core-shell spherical micelles. The spherical micelles are comprised of the phloretin hydrophobic core, the PLA hydrophobic middle layer, and the PEG hydrophilic shell. As the PEG5-b-PLA10 concentration increases, the Phloretin-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 PEG5-b-PLA10, PEG5-b-PLA15, PEG5-b-PLA20 copolymers demonstrate the ability to form well-organized core-shell configurations. PEG5-b-PLA10 exhibits a drug load of 0.08, which would be more appropriate to loading the phloretin drug, in comparison with the PEG5-b-PLA15 and PEG5-b-PLA20 systems. For PEG5-b-PLA10 system, the simulation results show that the suitable concentration of PEG5-b-PLA10 copolymer is 10-15%. These simulation results offer novel insights into the self-assembly process of Phloretin drug and PEG-b-PLA diblocks, elucidating the underlying physical mechanisms at the molecular level.