Dissipative particle dynamics simulations were performed to study the microstructures of doxorubicin (DOX) loaded/blank micelles self-assembled from cholesterol conjugated His 10 Arg 10 (HR20-Chol) at different pH conditions. DOX molecules can be efficiently encapsulated in the core of micelles. At pH>6.0, these micelles have stronger DOX loading ability due to the hydrophobicity of histidine residues, as compared to that of pH<6.0. With the decrease of pH from pH>6.0 to pH<6.0, the structure of micelles trends to be swelling from dense conformations. This structural transformation can facilitate the release of DOX from the core of micelles. All the simulation results are qualitatively consistent with the experimental results, demonstrating that the DPD method may provide a powerful tool in analysis and design of drug delivery systems.

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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.

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