Molecular Dynamics Simulation Of Composite Inorganic Drug Carrier Interface And Ibuprofen Diffusion

Because of stable physical-chemical property and abundant functionality, thecomposite inorganic drug carriers have attracted more and more concerns. Thestability and drug release properties of composite inorganic drug carriers are neededto focus, when we design and preparation of them. Therefore, the interfaceinteractions of composite inorganic drug carriers and the diffusion behavior of drug inthe drug carriers are one of the most important problems in composite drug carrierdesigning and synthesis area. However, the experimental researches could hardlyinvestigate these problems. Molecular dynamics simulation method as a computersimulation method is suitable for studying the above interface interaction anddiffusion process. It is a kind of deterministic simulation method, which strictlyfollows Newton’s equation of motion and the motions of all atoms accord with correctphysical laws. Therefore, the molecular dynamics simulation method is very suitablefor investigating the interface interaction and diffusion process. It can create atrajectory of all atoms in the simulation system which contains the dynamic quantitiesvarying with time will be generated and therefore the macroscopic properties(interaction energy, diffusion coefficient, etc.) can be calculated. In this paper, theMolecular dynamics simulation is employed to investigate the interface interaction ofseveral kinds of composite inorganic drug carriers and the drug diffusion process fromthe drug carrier. The main contents are as follow:(1) Fe3O4as a kind of biocompatible inorganic magnetic material is widely usedin preparing magnetic target drug carrier. The stability of interface between Fe3O4andother materials is the key factor about the stability of composite drug carrier. Becauseof the Fe3O4crystal is growth along the (111),(110) and (001) crystal faces, and thesurface anisotropy lead to the activity of three kinds of surface is different. Therefore,which surface have the highest activity interacting with the other materials need toconfirm before investigate the interface interaction of Fe3O4composite, which couldsimplify calculation on the premise of the result accurate and effective. Chitosan as a kind of natural biomedical materials is widely used to synthesis composite drugcarriers. It is benefits to test the interaction between the different surfaces of Fe3O4and chitosan, because there are many hydroxyl and amino groups on the chitosanmolecular chain. Chitosan has been used to calculate the interaction with the (111),(110) and (001) surfaces of Fe3O4by MD simulation. The interaction energy betweenchitosan and different Fe3O4surfaces indicates that the interaction between chitosanand Fe3O4(111) surface is much stronger than that of (110) and (001) surfaces. Itmeans that the Fe3O4(111) surface has the maximum activity and the chitosan mainlyinteracts with Fe3O4(111) surface. To sort out this discrepancy, the radial distributionfunction was used to compare and analyze the interaction between chitosan and Fe3O4(111) and (110) surfaces. The results show that the chitosan could interact with theoxygen and iron atoms on the Fe3O4(111) and (110) surfaces by hydrogen and aminogroups. But comparatively with the Fe3O4(110) surface, the stronger hydrogen bondsformed between the hydrogen and amino groups of chitosan and the oxygen atoms onFe3O4(111) surface, and the intermolecular forces between the hydrogen and aminogroups of chitosan and the iron atoms on the surface is stronger too. Therefore, theoxygen and iron atoms on Fe3O4(111) surface have the maximum activity. We usedFe3O4(111) surface to investigate the interaction between Fe3O4and other materialsin the chapters that follow.(2) The polymer composite with Fe3O4used in biomedical fields，there arealways two ways：Getting the Fe3O4particles into the polymer and wrapping thepolymer on the surface of Fe3O4particles. Any complex method, the stability ofinterface between polymer and Fe3O4would direct affect the properties of thecomposite materials. When this kind of composite materials used to drug carrier, themorphology of coating layer would also affect usability. Molecular dynamicssimulation was employed to investigate the interaction mechanism between six kindsof biomedical polymers (dextran, chitosan, poly lactide-glycolide acid, poly lactideacid, polyethylene glycol and polyethyleneimine) and Fe3O4(111) surface. Theinterface interaction energies and radial distribution functions implied that the interactions between Fe3O4(111) surface and the chitosan and dextran with hydrogenand amino groups are stronger than that of other polymers. Through analyzing thesimulation snapshots, concentration profiles and mean squrare displacements, themorphology of polymer on the Fe3O4(111) surface was decided by the peristalsisability of polymer chain. When the polymer chain has more rigidity (chitosan, dextran,polylactide acid etc.), the loose and porous structure of coating layer formed on theFe3O4(111) surface. When the polymer chain has more flexibility (polyethyleneglycol etc), the compact layer formed on the Fe3O4(111) surface. This study revealedthat when the biomedical polymer used to prepare polymer@Fe3O4composite drugcarriers, the polymer with hydrogen and amino groups and more rigidity molecularchain were beneficial to interface stability and drug load.(3) Fe3O4microsphere as a kind of biocompatible materials with high magneticresponse has the potential used to magnetic targeting drug delivery. Because of theirunique two-dimensional structure and good biocompatibility, graphene materials haveshown great potential applications in the drug delivery. The compsite between Fe3O4microsphere and graphene materials could have both drug loading and magnetictargeting. Molecular dynamics simulation was employed to investigate the interactionmechanism between graphene materials and Fe3O4(111) surface. And speculate thatthe adsorption behavior of grapheme materials onto the Fe3O4(111) surface.Combined with the interfacial interaction energy and radial distribution functionsanalysis, the stronger interaction between graphene oxide and Fe3O4(111) surfacethan that of graphene was mainly because strong interaction between the carboxylgroups of graphene oxide sheet edge and the surface. The simulation snapshotsindicated that when the graphene oxide and grapheme were introduced onto the Fe3O4(111) surface from parallel direction, the graphene oxide and graphene sheetsadsorbed on the surface smooth and the interfacial interactions were stronger. Welldistribution and great interfacial interaction energies show that the PEI was moreconducive to further modified the graphene oxide and graphene coating layer.Therefore, when design and prepare the graphene materials@Fe3O4microsphere composite drug carrier, using graphene oxide and suitable mixing speed to induce thegraphene oxide on the Fe3O4surface from parallel direction could obtain a compositedrug carrier with better performance. And the PEI could use to further modify forproviding more functions.(4) Capping the mesoporous silica materials is an effective method forcontrolling the drug release. Due to capping materials property constraints, the cappedmesoporous silica materials based composite drug carriers are often cappingincompletion. Graphene materials as soft two-dimensional materials can efficientlysolve the problems. Molecular dynamics simulation was employed to investigate theinterfacial interaction between four kinds of graphene materials and three kinds ofmesoporous silica materials. And used Au nanoparticle further modified the surface ofgraphene materials@mesoporous silica materials composite drug carriers. Thesimulation snapshots indicate that the graphene materials are capping the mesoporoussilica materials well. Combined with the interfacial interaction energy and radialdistribution functions analysis, the graphene oxide and reduced graphene oxideinteracted with the surface of mesoporous silica materials by hydrogen bond. Theamino and sulfydryl modified both could enhance the interfacial interaction betweengraphene oxide/reduced graphene oxide and mesoporous silica materials. Especiallythe interface of sulfydryl modified, not only the interfacial interaction energy washigher but also the disulfide bond with reducing response might be formed in theinterface under optimal condition. From the interface interaction energy andmorphological analysis, the introductin of Au nanoparticle not merely increased thefunctionality of composite drug carrier but also enhanced the stability of interface.Therefore, the graphene materials were suitable for capping the mesoporous silicamaterials. Especially, the sulfydryl modified graphene materials could form stabilityand reducing response interface with sulfydryl modified mesoporous silica materials.And the composite could be further modified easily by Au nanoparticle.(5) Mesoporous silica materials as a kind of commonly used drug carrier werewidely used in compositing with other materials for preparing multifunction drug carrier. And the drug load and delivery were in the charge of the mesoporous silicamaterials in these composite drug carriers. Investigation the diffusion process of drugin the mesoporous silica materials is of great importance in design the mesoporoussilica composite drug carriers. The MD simulation was used to study the diffusionprocess of model drug (ibuprofen) in MSMs under water environment based onmolecular scale. The results have proved that the ibuprofen diffused along the surfaceof MSMs pore channel during the whole diffusion process. And the interaction energybetween ibuprofen and the surface of MSMs pore channel is nearly constant in thediffusion. There were two key factors of affecting the ibuprofen diffusion: one factoris the interaction between ibuprofen and MSMs. The diffusion of ibuprofen would bedecelerated by the strong interaction between ibuprofen and the surface of MSMspore channel. Another factor is the diffusion rate of the water in the MSMs. Theibuprofen transport would be accelerated by the water with high diffusion rate. Andthe diffusion rate of water is concerned with the pore size of MSMs, big pore sizemeans high diffusion rate. Therefore, when we design and prepare the MSMscomposite drug carriers, we could obtain specific drug release rate by changing thepore size or the properties of pore channel.