Dissipative particle dynamics simulation on drug loading/release in polyester-PEG dendrimer

Polyester-PEG dendrimers are attractive for in vivo delivery of anti-cancer drug because of their biodegradability and low cytotoxicity. In this drug delivery system, G5-PEG polyester dendrimer is composed of hydrophobic polyester dendritic blocks and hydrophilic poly (ethylene glycol) (PEG), in which DOX molecules are efficiently encapsulated in the core of microspheres due to their affinity with G5 dendritic blocks. A dissipative particle dynamics (DPD) computational method was used to investigate the loading/release mechanism of anti-cancer drug doxorubicin (DOX) in G5-PEG polyester dendrimer. Four sequential transient stages were found during the drug encapsulation process: (1) all components distribute randomly in the cubic box at the initial stage, (2) DOX molecules dispersion in the G5-PEG dendritic microsphere, (3) amalgamation of the small core–shell dendritic microspheres into bigger ones, and (4) the stabilization stage. The loaded DOX content was calculated to be 16.7 % with a loading efficiency of 100 %, which is close to the experiment results (15.2 % DOX content with the loading efficiency of 99 %). The simulation also successfully revealed the drug release dynamics at pH 7.4 and pH 5 (37 °C). At pH 7.4, no DOX molecule was released from G5-PEG/DOX when only considered the influence of temperature on drug release. It demonstrates that the increase of system temperature (from 25 to 37 °C) is not the major factor for drug release at pH 7.4. When considered protonation of DOX at pH 5, it is benefit to generate some pores on the surface of G5-PEG/DOX microspheres, and the aperture of the pores increased with the simulation steps increased, which leads to the increasingly exposure of DOX molecules to water. However, the drug could not release toward the aqueous solution. It demonstrated that the protonation of DOX is not the major factor for the drug’s rapid release at pH 5 though it may facilitate the drug release process. Such results are in qualitatively consistent with the experimental observations and could provide valuable guidance in later design and optimization of this drug delivery system. The same tool could also be used to evaluate and design other similar drug/gene delivery systems.