Dissipative Particle Dynamics Studies of pH-Sensitive Tri-Block Copolymer Containing Zwitterionic Sulfobetaine As a Novel Anti-Cancer Drug Carrier

Dissipative particle dynamics (DPD) simulations were performed to study the microstructures and doxorubicin (DOX) loading/releasing in pH-sensitive amphiphilic triblock copolymer, composed of biodegradable hydrophobic poly(ε-caprolactone) (PCL), pH-sensitive poly (diethylaminoethyl methacrylate) (PDEA) and hydrophilic poly (sulfobetaine methacrylate) (PSBMA) / poly (ethylene glycol methacrylate) (PEGMA). Simulation results show that both PCL-PDEA-PSBMA and PCL-PDEA- PEGMA system would self-assemble into core-shell-corona micelles; with increasing copolymer concentration from 10% to 50% under the mass ratio of copolymer to drug as 10:3, the morphologies formed by PCL-PDEA-PSBMA and DOX remains spherical micelles even though adhesion at a certain direction is observed at high concentration, but PCL-PDEA-PEGMA undergoes the transition from spherical to cylindrical and finally to lamellar micelles. Though both two copolymer systems can self-assemble into core-shell-corona micelles under a proper condition, the inner structures are quite different. The shell layers formed by PEGMA micelles are inhomogeneous in size due to the amphiphilicity of PEG; while shell layers in PCL-PDEA-PSBMA micelles are homogenous because of strong hydrophilicity of the zwitterionic PCB. The phenomenon indicates that PSBMA is more stable than PEGMA. In particular, the micelles exhibit pH dependency as a result of the protonation of the PDEA block，resulting in the instantaneous releasing of DOX. What’s more, the releasing process follows the swelling-demicellization-releasing mechanism. In order to moderate the micelle’s drug loading efficiency, in vivo stability and drug release effect, PCL-PDEA-PSBMA/PEGMA copolymer with the block ratio at 20:20:20, while the concentration remains 10% and DOX remains 3% is considered to be the best. The integration of simulation might be a valuable method for the optimization and design of biomaterials for drug delivery with desired properties.