Preparation And Drug Release Properties Study Of Chitosan Composite Microcapsules

Chitosan is a kind of natural macromolecule material with abundant source in nature.The microcapsule with chitosan as wall material has a very important application in the field of drug delivery and controlled release.However,pure chitosan microcapsules have poor mechanical properties and can only be loaded with hydrophilic drugs.In this paper,in order to improve the mechanical properties of chitosan microcapsules,and to achieve the load of hydrophobic drugs at the same time,novel functionalized chitosan composite microcapsule are prepared by introducing biocompatible graphene into the wall and cyclodextrin with hydrophobic cavity in the chitosan chain.In the first part of this paper,reduced graphene oxide(rGO)sheets were first modified with 2-hydroxypropyltrimethyl ammonium chloride chitosan(HACC).Based on the electrostatic interaction between HACC-rGO,chitosan(CS)and sodium lauryl sulfate(SDS),the monodisperse CS/ HACC-rGO microcapsules were prepared by gas-liquid microfluidic device.At the same time,the effects of gas flow rate and HACC-rGO on the particle size and distribution of microcapsules were investigated.The morphology and structure of CS/ HACC-rGO microcapsules were characterized by scanning electron microscopy(SEM),X ray diffraction(XRD)and thermogravimetric analyzer(TGA).The results showed that the size of microcapsules was decreased with the increase of gas flow rate,and in low gas flow rate(< 0.75L/min),microcapsules with a narrow particle size distribution,are monodisperse The introduction of HACC-rGO can play a role of physical crosslinking point,so that the mechanical properties of the microcapsule wall can be greatly improved.Hydrophilic drug sodium salicylate as a model drug was loaded into CS/ HACC-rGO microcapsules.The results showed that the introduction of HACC-rGO slowed the release rate of the drug,and increased the release period of the drug.When the release medium was 1.0wt% ?-CD,the CS/ HACC-rGO microcapsules remained original shape,indicating that the introduction of HACC-rGO enhanced the chemical stability of the microcapsules to ?-CD.MTT was used to test the cytotoxicity of HACC-rGO microcapsules in vitro,and the cells maintained a high survival rate.The results showed that CS/ HACC-rGO microcapsules have no toxicity.In the second part of this paper,using maleic anhydride as bridge bond,?-CD was grafted onto chitosan molecular chain to obtain water-soluble chitosan modified cyclodextrin(CS-MAH-?-CD).Then,CS-MAH-?-CD as the wall material,the monodisperse CS-MAH-?-CD /HACC-rGO microcapsules were prepared by gas liquid microfluidic device.Due to the introduction of the ?-CD group,it can bind with the hydrophobic drug binding,which increases the loading capacity of the system.The drug loading and release of CS-MAH-?-CD/HACC-rGO microcapsules were studied with poorly water-soluble 5-fluorouracil as the model drug.The results showed that the introduction of the ?-CD group significantly increased the loading capacity of the microcapsules to the hydrophobic drugs and delayed the release rate of the drug.Based on the load capacity of chitosan to hydrophilic drug,and the introduction of cyclodextrin groups can improve loading capacity of hydrophobic drugs,so it can be realized to be loaded with hydrophobic drugs and hydrophilic drugs in CS-MAH-?-CD microcapsules to construct a dual-drug delivery system.