Preparation Of Cellulose Gel Microspheres And Its Application In Hemoperfusion

One of the most important principles for solute clearance with hemoperfusion is adsorption. The curative effect of hemoperfusion depends on the particular function of adsorbents. Reseachers all over the word have been involving in the study of adsorbents with high adsorption performance, low nonspecific adsorption and good biocompatibility. The research of biomedical adsorbing materials has become a hot study problem in both biomedicine and material science. Cellulose is the most abundant renewable resources in the world and it will bring enormous social and economic benefits once applying cellulose microspheres to hemoperfusion therapy. In this article cellulose was rapidly dissolved with Na OH/urea/H2 O at low temperature and cellulose microspheres were prepared by inverse suspension cross-linking method. immunoadsorbent and endotoxin adsorbent were synthesized with cellulose microspheres as base material while protein A and polymyxin B as ligand respectively. The adsorption properties for Ig G and endotoxin in human plasma were evaluated.Cellulose was rapidly dissolved with Na OH/urea/H2 O at low temperature and cellulose microspheres were prepared with epichlorohydrin as crosslinker. We could obtain cellulose microspheres with both good sphericity and dispersion when the amount of epichlorohydrin ranged from 3 % to 8 %(epichlorohydrin/cellulose solution, by volume). 60.5 wt% of cellulose microspheres with particle size distribution from 50 μm to 200 μm could be obtained under such optimum conditions as 5 % of epichlorohydrin amount, 450 rpm of agitation speed, 5 % of span 80 content and 3:1 of oil-water ratio. Emulsifying agent content was the most influential factor of particle size and then was in sequence of oil-water ratio and agitation speed.Protein A-based immunoadsorbent was prepared by using cross-linked cellulose microspheres as the media which were activated by Na IO4, epichlorohydrin and 1, 4-butanediol diglycidyl ether respectively and recombinant protein A as the ligand. The static and dynamic adsorption properties for Ig G in human plasma were studied. Protein A-based immunoadsorbent synthetized by Na IO4 could achieve maximum static binding capacity of 23 mg/g and dynamic binding capacity of 13 mg/g with the protein A density of 6.81 mg/g. Adsorption equilibrium could be reached within 50 min. While adsorbent synthetized by 1,4-butanediol diglycidyl ether showed better adsorption performance than which synthetized by Na IO4 and epichlorohydrin. The results showed that the maximum of static and dynamic adsorption capacity of Ig G were 38 mg/g and 18 mg/g respectively. Besides, the adsorbents showed excellent adsorption selectivity for Ig G in human plasma.Endotoxin adsorbent was synthetized by using 1,4-butanediol diglycidyl ether to activate cross-linked cellulose gel and then coupling PMB as ligand. The adsorption kinetics and isotherm for endotoxin in physiologic saline solution were discussed. Effect of initial concentration of endotoxin, gel-plasma ratio and adsorption time on static adsorption efficiency and plasma perfusion rate on dynamic adsorption properties of endotoxin in human plasma were also taken into account. The results of endotoxin adsorption in physiologic saline solution revealed that the adsorption kinetic was accorded with the second order equation and the adsorption equilibrium could be reached within 40 min. Adsorption behavior fitted the Langmuir model, and the maximum adsorption capacity was 3605.1 EU/g. The adsorption experiments in human plasma revealed that adsorption equilibrium time was 80 min and the best gel-plasma ratio was 1:10. The adsorbent could reach a high endotoxin clearance of 71 % at an initial endotoxin concentration of 5 EU/m L which indicated that the synthetized adsorbent had excellent adsorption performance for endotoxin, meanwhile the adsorbents showed good dynamic adsorption performance and low non-specific adsorption with the adsorption rate of plasma protein less than 10%.In this article cellulose microspheres were prepared successfully with Na OH/urea/H2 O as the solvent which was simple and cheapness. Adsorbents prepared by using cellulose microspheres as media were applied to blood purification and showed good adsorption performance which indicated a very wide application prospect in clinic.