4/6-Herto-arm and 4/6-mikto-arm star-shaped block polymeric drug-loaded micelles and their pH-responsive controlled release properties: a dissipative particle dynamics simulation

Star-shaped polymers have received significant attention and have been widely developed for prospective applications in drug delivery owing to their topological structure and unique physiochemical characteristics. The anticancer drug doxorubicin (DOX) was used as a model drug, and four/six-arm star-shaped block polymeric micelles were employed as the carriers. The dissipative particle dynamics (DPD) method was adopted to simulate the formation of micelles, the effects of the hydrophobic/hydrophilic block ratio on the micellar structure and drug-loading performance, the effect of the drug loading content on the micellar morphology, and the effect of the pH-sensitive block ratio on the drug release properties. Under neutral conditions (pH = 7.4), increasing the hydrophobic block ratio reduces the stability of the micelle structure but could improve its drug loading performance. Increasing the pH-sensitive block (DEAEMA) ratio is beneficial to the drug loading performance of the mikto-arm star-shaped polymeric micelles and is detrimental to the drug loading performance of the herto-arm star-shaped polymeric micelles. After comparing the structural changes, radial distribution function (RDF) and mean square displacement (MSD) of the polymeric micelles with different pH-sensitive block ratios under weakly acidic conditions (pH = 5.0), the drug release properties of the drug-loaded micelles were systematically analysed. The results showed that the higher the proportion of the pH-sensitive block in the polymeric micelles, the better their pH-response performance, and the looser the structure of the micelles during the release process. A too high or too low ratio of pH-sensitive blocks in the polymeric micelles was detrimental to drug release performance. This study could provide theoretical support for the structural design and development of novel functional block polymers.