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

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-<i>b</i>-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-<i>b</i>-PLA copolymers and model drug in aqueous environments, utilizing dissipative particle dynamics simulations. Our simulations show that drug and PEG-<i>b</i>-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 PEG₅-<i>b</i>-PLA₁₀concentration increases, the drug-loaded PEG-<i>b</i>-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-<i>b</i>-PLA₁₀, PEG₅-<i>b</i>-PLA₁₅, PEG₅-<i>b</i>-PLA₂₀copolymers demonstrate the ability to form well-organized core-shell configurations. PEG₅-<i>b</i>-PLA₁₀exhibits a drug load of 0.08, which is better suited for drug loading, in comparison with the PEG₅-<i>b</i>-PLA₁₅and PEG₅-<i>b</i>-PLA₂₀systems. For PEG₅-<i>b</i>-PLA₁₀system, the simulation results show that the suitable concentration of PEG₅-<i>b</i>-PLA₁₀copolymer 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-<i>b</i>-PLA diblocks, elucidating the underlying physical mechanisms at the molecular level.