Dissipative Particle Dynamics Studies of Doxorubicin-Loaded Micelles Assembled from Four-Arm Star Triblock Polymers 4AS-PCL-b-PDEAEMA-b-PPEGMA and their pH-Release Mechanism

Abstract

Dissipative particle dynamics (DPD) simulation was applied to investigate the microstructures of the micelles self-assembled from pH-sensitive four-arm star triblock poly(ε-caprolactone)-b-poly(2-(diethylamino)ethyl methacrylate)-b-poly(poly(ethylene glycol) methyl ether methacrylate) (4AS-PCL-b-PDEAEMA-b-PPEGMA). In the optimized system, the micelles have a core-mesosphere-shell three-layer structure. The drug-loading process and its distribution at different formulations in the micelles were studied. The results show that DOX molecules distributed in the core and the interface between the core and the mesosphere, suggesting the potential encapsulation capacity of DOX molecules. More drugs were loaded in the micelles with the increase in DOX, and the size of micelles became larger. However, some openings start to generate on the PEG shell when the DOX reaches a certain concentration. By changing the pH values of the system, different morphologies of the micelles were acquired after the pH-sensitive blocks PDEAEMA were protonated, the mechanism of which was also analyzed through correlating functions. The results indicated that the sudden increase in solubility parameter of the pH-sensitive blocks and the swelling of the micelles were the key factors on the change of morphologies. Furthermore, with the decrease in pH value, the number and size of the cracks on the surface of the micelles were larger, which may have a direct effect on the drug release. In conclusion, 4AS-PCL-b-PDEAEMA-b-PPEGMA has great promising applications in delivering hydrophobic anticancer drugs for improved cancer therapy.

Mesoscopic simulation studies on the formation mechanism of drug loaded polymeric micelles

“…The formation mechanism of drug delivery carriers in an aqueous environment can be investigated in greater detail through mesoscopic simulations than through experimentation [19]. Among usual mesoscopic simulation methods, for instance molecular dynamics (MD) simulation whose time scales are too short to observe the formation of the micelles, and the simulation at atom level is also very expensive [20][21][22], dissipative particle dynamics (DPD) which allows for a much larger time step and length scales is widely used in the simulation of coarse-grained models of fairly complex systems [23,24]. Recently, DPD simulations become a systematic and efficient method to explore the microstructure and the formation mechanism of polymeric micelles [25][26][27].…”

Structure–property relationship of pH‐sensitive (PCL)2(PDEA‐b‐PPEGMA)2 micelles: Experiment and DPD simulation

“…[22][23][24][25] In our recent work, DPD simulation study was carried out on the formation of DOX-loaded polymeric micelles formed by pH-sensitive amphiphilic homo-arm star polymer in neutral environment, effect of DOX content on morphologies of micelles, effect of pH value on morphologies of blank and DOX-loaded micelles, and so forth, which was without sufficient experimental results as a background. 26 Herein, the pH-sensitive amphiphilic A 2 (BC) 2 miktoarm star polymers (PCL) 2 (PDEA-b-PPEGMA) 2 with different block ratios were synthesized and used as an integrated platform for intracellular delivery of the anticancer drug DOX. Their selfassembled spherical micelles were composed of PCL core, pH-sensitive PDEA mesosphere, and poly (ethylene glycol) methyl ether methacrylate (PPEGMA) shell.…”

Computational Amphiphilic Materials for Drug Delivery

“…However, the drug-loaded micelles did not exhibit any drug release at different pH values. This was attributed to the fact that stirring is usually applied in experiment but not incorporated in the simulation (Nie et al, 2013). They also investigated the effectiveness of drug distribution in pH-sensitive AlBmCn copolymers with different lengths of hydrophilic block, pH-sensitive block and hydrophobic block.…”