DPD simulations on morphologies and structures of blank PLGA-b-PEG-b-PLGA polymeric micelles and docetaxel-loaded PLGA-b-PEG-b-PLGA polymeric micelles

Dissipative particle dynamics (DPD) simulation was used to study the morphologies and structures of blank (no drug) poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (PLGA-b-PEG-b-PLGA) polymeric micelles and the docetaxel (Dtx)-loaded PLGA-b-PEG-b-PLGA polymeric micelles. We focused on the influences of PLGA-b-PEG-b-PLGA copolymer concentration, composition, Dtx drug content and the shear rate on morphologies and structures of the micelles. Our simulations show that the PLGA-b-PEG-b-PLGA copolymers in the aqueous solutions could aggregate and form blank micelles while Dtx drug and PLGA-b-PEG-b-PLGA could aggregate and form drug-loaded micelles. Under different PLGA-b-PEG-b-PLGA concentrations and drug content, the blank and drug-loaded micelles are observed as spherical, onionlike, columnar, and lamellar structures. The onionlike structures are comprised of the PEG hydrophilic core, the PLGA hydrophobic middle layer, and the PEG hydrophilic shell. As the structure of micelles varies from a spherical core–shell structure to a core–middle layer–shell onionlike structure, the distribution of the Dtx drugs diffuses from the core to the PLGA middle layer of the aggregate. In addition, the drug release process of the Dtx-loaded micelles under shear flow is also simulated. And the results show that the spherical micelles turn into a columnar structure under a shear rate from 0.2 to 3.4. When the shear rate increases to 3.5, the Dtx drugs released gradually increase until all are released with time evolution. These findings illustrate the dependence of the structural morphologies on the detailed molecular parameters of PLGA-b-PEG-b-PLGA and Dtx.