Computer Simulations on the Anticancer Drug Delivery System of Docetaxel and PLGA-PEG Copolymer

Molecular dynamics (MD) and dissipative particle dynamics (DPD) simulations were integrated to study the morphologies of the drug delivery system self-assembled by amphiphilic block copolymer poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-PEG) and anticancer drug docetaxel. In this work, the solubility parameters used in DPD simulations were calculated by MD simulations. In DPD simulations, the effects of copolymer concentration, copolymer composition and drug content on self-assembled morphologies were investigated. Simulation results show that the morphologies self-assembled by PLGA-PEG and docetaxel (Dtx) undergo the transition from spherical to cylindrical and finally to lamellar micelles when increasing the copolymer concentration from 10% to 50% while maintaining the mass ratio of copolymer to drug as 5 :1. In all cases, core-shell structures were obtained with the hydrophobic PLGA as the core and the hydrophilic PEG as the shell. It is found that PLGA-PEG copolymer with the composition of PEG block ranging from 10% to 90% (the total number of the blocks of PLGA-PEG is kept as 100) self-assembles into spherical core-shell structures in aqueous solutions without drug when the copolymer concentration is 10%. When the mole fraction of PEG in PLGA-PEG copolymer is less than 20%, PEG is unable to pack PLGA completely. With the increase of mole fraction of PEG, the PEG shell becomes thicker and the size of the core becomes smaller. In order to moderate the micelle's drug loading efficiency (a small PLGA core will load small amount of hydrophobic anticancer drug Dtx) and stability (a thin PEG shell may make the core-shell micelle unstable), PLGA-PEG copolymer with the molar ratio of PEG to PLGA as 40 : 60 is considered to be the best drug carrier candidate. Besides, the simulation results show that the content of drugs also affects the self-assembled structure. When the drug content is under a certain value, spherical core-shell structures are gained and the size of them grows up with the increase of the drug content. When the drug content is above that value, the spherical structures will connect each other to form cylindrical structures. Considering the advantage of spherical core-shell structures in drug delivery, the optimal mass ratio of docetaxel, PLGA(40)-PEG(60) copolymer and water is 5 :10 : 90. This work is expected to provide some guidance for the design and development of drug delivery systems.