The microstructures of doxorubicin-loaded micelles prepared from block polymers His(x)Lys10 (x = 0, 5, 10) conjugated with docosahexaenoic acid (DHA) are investigated under different pH conditions, using dissipative particle dynamics (DPD) simulations. The conformation of micelles and the DOX distributions in micelles were obviously influenced by pH values and the length of the histidine segment. At pH >6.0, the micelles self-assembled from the polymers were dense and compact. The drugs were entrapped well within the micellar core. The particle size increases as the histidine length increases. With the decrease of pH value to be lower than 6.0, there was no distinct difference for the micelles self-assembled from the polymer without histidine residues. However, the micelles prepared from the polymers with histidine residues shows a structural transformation from dense to swollen conformation, leading to an increased particle size from 10.3 to 14.5 DPD units for DHD-His10Lys10 micelles. This structural transformation of micelles can accelerate the DOX release from micelles under lower pH conditions. The in vitro drug release from micelles is accelerated by the decrease of pH value from 7.4 (physiological environment) to 5.0 (lysosomal environment). The integration of simulation and experiments might be a valuable method for the optimization and design of biomaterials for drug delivery with desired properties.
Keywords: dissipative particle dynamics simulation; drug delivery; drug distribution; drug release; pH-sensitive micelle.