Mesoscale Behaviors Of Polymeric Micelles: Insight From Dissipative Particle Dynamics Simulation

Polyelectrolyte onion-type micelles and unimolecular micelles formed from polymers have unique internal hierarchical structure and thermodynamic stabled micellar structure respectively,which can improve the water solubility and oral bioavailability of the loaded drug,thus it is prospective to apply them in novel drug delivery system.This project utilized computer simulations based on experimental researches and theoretical analysis to investigate the microscopic/mesoscopic behavior and structure of polyelectrolyte self-assembled onion-type micelles and unimolecular star-like block copolymer micelles.Some relevant design rules and regulations have been proposed from qualitative aspect,which could provide a novel approach for the development of self-assembled micelles in drug delivery systems.Dissipative particle dynamics(DPD)simulation was used for the first time to explore the self-assembling mesoscale behavior of onion-type micelles formed by polyelectrolyte blends,which consist of anticoagulant polyanionic fondparinux(Fpx)and cationic derivatives squalenoyl(CSq,including Sq+ and Sq++).Simulation results indicated that the proportion of the components,hydrophobic block length of CSq and solution concentrations greatly influence the mophorlogies of the polyelectrolyte self-assemblies.Based on the simulation results,the formation process and mechanism of onion-type micelles were discussed,which is attributed to the joint effect of the non-bonded interaction provided by the polar groups between Fpx-CSq and the hydrophobic interaction contributed by the hydrophobic chain of CSq.This study offers a theoretical guide to control the morphologies of onion-type micelles and paves the way towards the design of novel nanoparticulate drug carriers with tailored onion-type structures developed by ion pairing approach.A unimolecular micelle system formed from star-like block copolymers ?-CD-g-(PLA-bPDMAEMA-b-PEtOx MA)in aqueous media was investigated by DPD simulations to explore the formation process of unimolecular micelles.The simulation results showed that using longer hydrophobic or pH-sensitive chains,shorter hydrophilic backbones,smaller hydrophilic side chain grafting density,and fewer polymer arms can enhance hydrophobic interactions between the polymer molecules or weaken hydrophilic interactions.This disrupts the hydrophilic-lipophilic balance and results in the aggregation of unimolecular micelles.Furthermore,this unimolecular polymeric micelle could be used for encapsulating gold nanoparticles and anticancer drug DOX,whose mesoscopic structure were also explored.The unimolecular micelles were capable of impeding gold nanoparticle aggregation and controlling the particle size.While the drug delivery will be affected because of the aggregation of unimolecular miscelles caused by overhigh drug concentration in the system.This study provides important guidelines for the design and preparation of unimolecular polymeric micelles with desired performance for drug delivery.