Fabrication And Properities Of Hydrogel/ Microsphere/ ICA Composite Drug Delivery System

Scaffold material is known as the center of tissue engineering, which can not only provide structural support for cells, but also have effect on guiding tissue regeneration and control the structure of the new tissue. Therefore, it is important to find a scaffold material which can not only provide excellent biocompatibility and biodegradability, but also have a good machinability with three-dimensional pores structure, in the study of tissue engineering.Both of gelatin and hyaluronic acid are natural biological materials, which are commonly used to fabricate the vector of drug release, because of their good hydrophilicity, biocompatibility and biodegradability, etc. Icariin is the main effective component of flavonoids, which was extracted from the stem leaf of epimedium. In recent years, a large number of pharmacological studies have shown that ICA can promote the proliferation and differentiation of osteoblast. The hydrogel/microsphere/ICA composite system was prepared through hybrid method with microspheres/ICA loaded on Gel/HA hydrogel, in turn to expand the application of hydrogel.Composite microspheres based on Gel and HA were prepared by an emulsion-coagulation method with glutaraldehyde as a cross-linker. The influences of stirring speed, cross-linker concentration, hyaluronic acid content and water/oil ratio on the particle size and surface morphology were investigated. The FTIR spectra characterization indicated that Gel and HA were cross-linked successfully by the glutaraldehyde. The results showed that the adhesion and agglomeration phenomena were apparent when the HA content reached 10.0 wt%. The particle diameter of the microspheres decreased greatly with increasing stirring speed; however, the adhesion of smaller microsphere could be observed when the stirring speed reached 800 rpm. The effect of cross-linker concentration on the particle size was not significant but the dispersion degree of the Gel/HA microspheres decreased with decreasing cross-linker content. The particle size of the microspheres gradually became uniform with the increase of the water/oil ratios. The dispersion and surface smoothness level could be improved by optimizing the experimental conditions. The composite microspheres with different morphology could be fabricated though different post-processing methods. Washing the microspheres with acetone water solution with a volume ratio 3:1 and natural drying, then the microspheres showing a smooth surface; washing the microspheres with pure acetone and natural drying, the microspheres became corrugated; washing the microspheres with acetone water solution with a volume ratio 3:1 and freeze-drying, the microspheres showed obvious three-dimensional porous structure.In this study, the Gel/HA hydrogel was prepared by freeze-drying method with EDC as a cross-linker. The FTIR spectra characterization indicated that the new ester and amide keys were formed between Gel and HA. The pore diameter of the composite scaffold was 100-400μm. There were many hydrophilic group exist in the molecular chains of HA, therefore, the hydrophilicity of the composite scaffold could be improved with the use of HA; the hydrogel showed a interconnected three-dimensional porous structure, the aperture size is about 100-400μm under the SEM; Increasing the proportion of HA could increase the swelling ratios and decrease the WVTR of hydrogel.The ICA/microsphere/hydrogel composite system was prepared through hybrid method with ICA/Gel/HA microspheres loaded on Gel/HA hydrogel. The influences of cross-linker concentration, the dosage of microspheres and the particle size of microspheres on the structure and morphology were investigated. The results showed that the density of composite system increased with the increasing cross-linker content; Once the dosage of microspheres was more than 50%, the pores wall were gone to be collapsed, even the three-dimensional porous structure of composite system would be destroyed; Bigger size of the microspheres would lead worse combination of the hydrogel and microspheres. The pores wall of composite system were destroyed, the microspheres fell off gradually, the three dimensional structure were collapsed gradually, during the degradation process.Microspheres/ICA, hydrogel/ICA and hydrogel/microspheres/ICA were prepared by physical composite. The functional group, morphology and structure, swelling degree, drug-loading rate, entrapment rate and vitro release performance of those drug release system were respectively studied through FTIR, SEM and UV. The results showed that ICA was successfully loaded on those vectors, and that had little impact on the morphology; Both of the drug-loading rate and the entrapment rate were negatively related to the concentration of cross-linker and the microspheres particle size, but positive related to the concentration of ICA; The vitro release performance significantly decreased with the increase of cross-linker concentration,increase with the decrease of the microspheres’ particle size and he increase of ICA concentration. The releasing rate of ICA in hydrogel/ICA system was too fast to control. A three-dimensional drug delivery system with controlled release rate could be prepared through regulation the concentration of cross-linker and the particle size of microspheres.