چكيده به لاتين
Abstract
In order to provide the means to predict from molecular dynamics (MD) simulations the structures of copolymer-based micelles in solution, we developed coarse grain force field (CGq FF) parameters for polyethylene glycol (PEG), for poly ε-caprolactone (PCL) as well as diblock PEG-b-PCL and triblock PEG-b-PBO-b-PCL copolymers. We illustrate the application of these CG-FF by following the formation of a spherical micelle from 250 chains of different compositions of PEG-b-PCL and PEG-b-PBO-b-PCL block copolymers (with different hydrophilic to hydrophobic portions) in water over 2 microseconds of MD. A key advance here is the use of quantum mechanics to train the parameters describing the non-bonded interactions between the CG beads. The functional forms are the same as the MARTINI CG force field (FF) so standard MD codes, such as GROMACS, can be used. Our CG-FF parameters reproduce such structural properties as density, radius of gyration (Rg), and end-to-end distance (h) from both experiment and from All Atom (AA) and United Atom (UA) simulations. We also describe well the experimentally observed behavior for the polymer-air and polymer-water interfaces. This coarse grain model also precisely describes the structural properties, the self-assembly mechasim, the drug loading and the thermodynamic stability of each micelle system in aqueous media. The CG simulation results show that the smallest system based on the deblock copolymer of PEG23-b-PCL9, results in a semi-spherical micelle which remains stable until the end of the simulation time (2µs). The drug loading capacity and efficiency of this system for DOX is 14.8 % and 5% respectively.
We further found that the two shorter diblock and triblock systems show similar self-assembly processes, both resulting in slightly prolate-spheres, while the longer diblock system undergoes a morphological transition from an intermediate rod-like micelle to a prolate-sphere, while the micelle formed from the longer triblock system, MePEG45-b-PBO9-b-PCL61, with a short PBO inserted between the hydrophilic and hydrophobic sections, results in a stable rod-like micelle.
Keywords: Diblock Copolymer, Self-assembly, Micelle, Drug Loading, Molecular Dynamic Simulation, Coarse Grain Force Field, Quantum Mechanic Calculation, Thermodynamic Stability
