Mesoscopic simulations on the aggregation behavior of pH-responsive polymeric micelles for drug delivery

Computer simulations, dissipative particle dynamics (DPD) and mesoscopic dynamics (MesoDyn), are performed to study the aggregation behavior of pH-sensitive micelles self-assembled from amphiphilic polymer poly(methyl methacrylate-co-methacrylic acid)-b-poly(poly-(ethylene glycol) methyl ether monomethacrylate), P(MMA-co-MAA)-b-PPEGMA. Ibuprofen (IBU) is selected as the model drug. It can be seen from DPD simulations that P(MMA-co-MAA)-b-PPEGMA and IBU form spherical core–shell micelles at certain compositions, and IBU molecules distribute inside the core formed by hydrophobic MMA. The polymer molecules aggregate first, and then IBU diffuses into the aggregate, forming drug-loaded nanoparticles. With different compositions of polymer and IBU, aggregate morphologies in water are observed as sphere, column and lamella. From MesoDyn results, with less hydrophobic MMA beads, the polymer chains are more difficult to form ordered aggregates, and the order parameters get equilibrated in a longer time. The pH value also affects the aggregate process. At pH < 5, the polymer could form traditional core–shell micelles. But at pH > 5, the morphology of micelles is found to be anomalous and loose for releasing drug. MAA aggregates on the surface, instead of the inside. The simulation results are qualitatively consistent with the experimental results.

At pH < 5, the P(MMA-co-MAA)-b-PPEGMA self-assembled micelle is sphere and phase separation is easy. At pH > 5, the micelle is anomalous and loose, resulting in fast release of drugs.Figure optionsDownload high-quality image (100 K)Download as PowerPoint slideHighlights
► The formation of drug-loaded polymeric micelles undergoes three stages.
► The special morphologies are sphere, column and lamella at different compositions.
► Less hydrophobic segments in polymer enhance difficulty to form ordered aggregates.
► At pH > 5, the micelles are anomalous and loose, facilitating the release of drugs.