Self-Assembled Polymeric Micelles For Drug Delivery System: Insight From Dissipative Particle Dynamics Simulation

pH sensitive drug-loaded micelles and multilamellar nanoparticles self-assembled from polymers are capable of effectively improving water solubility and oral bioavailability of the drug loaded, controlling drug release, thus they have prospective application for novel drug delivery systems. This work employed computer simulations based on experimental researches and theoretical analysis to investigate the relationship between structure and performance of polymeric micelles in several case studies, which could provide a novel approach for the development of self-assembled micelles in drug delivery systems.The performance of self-assembled polymeric micelles is closely related to the structure of polymers. In Section Two, dissipative particle dynamics(DPD) simulation is carried out on four(PCL)2(PDEA-b-PPEGMA)2 polymers with different block ratios and their micelles. The miktoarm star polymers are assembled into spherical micelles composed of PCL core, pH-sensitive PDEA mesosphere and PPEGMA shell in neutral condition. The micelles formed from the polymers are with different structures, and their drug distributions are various. Morphology transformation of micelles is found in acidic condition, and the pH response mechanism is studied in depth by radial distribution function and mean square radius of gyration. At last, the structure-property relationships of the polymers are proposed combining the simulation and experiment results. The results demonstrate that this type of pH-sensitive micelles could be used as an efficient carrier for hydrophobic anticancer drugs, achieving controlled and sustained drug release.How to control the release of drugs from pH-sensitive polymeric micelles is an issue of common concern, which is important to the effectiveness of micelles. The components and properties of polymers can notably influence drug distributions inside micelles which is a key factor affecting drug release from micelles. In Section Three, DPD simulation method is firstly used to study the structural transformation of micelles during the protonation process and drug release process from micelles with different drug distributions. And the effects of the length of polymer blocks and drug structure on drug release are also studied. Some design principles of pH-sensitive polymers for drug delivery are proposed according to the simulation results. This work is in favor of establishing qualitative rules for the design and optimization of congener polymers for desired drug delivery, and providing a potential approach for the development of new multiblock pH-sensitive polymeric micelles.Multilamellar nanoparticles(NPs) can be formed from mixing two components with opposite charges through self-assembly for drug delivery. To explore the details of NPs association and mechanism can help develop multilamellar NPs formed by charged blends through self-assembly for drug delivery. In Section Four, we use DPD simulation for the first time to determine the structure-property relationship of multilamellar NPs formed by charged blends through ion pairing approach. As a case study, the system with polyanionic fondparinux(Fpx) and cationic derivatives squalenoyl(CSq, including Sq+ and Sq++) in aqueous media is investigated, with a focus on the impact of optimized formation condition and mechanism of regular spherical multilamellar NPs. In particular, we find that highly ordered multilamellar structures tend to form with the joint effect of electrostatic interaction between Fpx-CSq and hydrophobic interaction contributed by CSq.