Preparation And Drug Loading Performance Of Dextran Hydrogel Microsphere

Hydrogels are there-dimensional polymeric networks that capable of imbibing large amount of water or biological fluids while remaining insoluble in aqueous solutions.Polysaccharide-based microgels with high water content,excellent biocompatibility and controllable particle size have been widely studied as carrier material for drug release and delivery.The morphology and particle size of hydrogel microparticles can strongly affect their performance and application as biomaterials.Dextran is a natural polymer with excellent biocompatibility,which can be easily functionalized through its reactive hydroxyl chemistries.In order to prepare dextran microgel with controllable size and morphology,microemulsion polymerization and crosslinking techniques have been widely used.In this study,dextran microgel with particle size from 400 nm to 70 μm can be prepared with the CYH/Span 80-Tween 80/Dex-CHO emulsion system.Doxorubicin(DOX)was used as the drug model to study the loading,pH-triggered release characteristics of doxorubicin-dextran microgel.The main contents are as follows:1.Aldehyded dextran(Dex-CHO)was synthesized by the periodate oxidation of dextran in aqueous solution of sodium periodate.The degree of oxidation was determined by hydroxylamine hydrochloride titration.The results showed that aldehyde content on Dex-CHO was 6.37±0.015 mmol/g and oxidation degree of dextran was(117.60±0.08)%,which proved that the dextran was partially oxidized.Furtherly,the optimum reaction conditions for Dex-CHO crosslinking were explored.The results showed that a relatively uniform and compact milky white hydrogel were prepared when n-NH2/n-CHO=0.52.Dex-CHO solutions with higher concentration turn into gel faster than those with lower concentration.The crosslinking condition is better when Dex-CHO solution with polymer concentration was 75 mg/mL.However,Dex-CHO solution with polymer concentration less than 50 mg/mL were no longer crosslinked to form a hydrogel.2.A series of dextran microgel were prepared by the inverse microemulsion technique.And,effects of the HLB value,emulsification method,volume ratio of water to oil(φ),molar ratio of water to emulsifier(R0)on the morphology and particle size of the dextran microgel were investigated,The results indicated that dextran microgels with particle size from 400 nm to 70 μm can be prepared with the CYH/Span 80-Tween 80/Dex-CHO emulsion system.Microgels prepared under ultrasonic have smaller particle size than that prepared under mechanical agitation.Dextran microgel with relatively small diameter at～422 nm was obtained with m(Tween 80)/m(Span 80)=0.10,HLB=5.27,φ=1/6.In addition,the particle size of the dextran microgel increased with the increase of the R0 value.3.Properties and release profile of dextran microgel as drug delivery system was evaluated using Doxorubicin(DOX)as the drug model.The prodrug was obtained by the condensation reaction of the aldehyde group(-CHO)on the oxidized dextran with the amino group(-NH2)on DOX to form a Schiff base linkage,and then crosslinked in the inverse microemulsion to prepare the DOX loaded dextran microgel(Dex-DOX microgel).Notably,the maximum of loading efficiency(LE%)was calculated about 32.66%as the DOX·HCl concentration was 4mg/mL,and the resulted Dex-DOX microgel have relatively smaller diameter of 736.2 nm.In addition,particle size of the Dex-DOX microgel increased compared with that of dextran microgel without drug loading,the Zeta potential was slightly decreased and the absolute value was～25 mV,indicating that the DOX loaded dxtran microgel was relatively stable in aqueous solution.The results of in vitro release profile showed that the release of doxorubicin in Dex-DOX microgel was pH-responsive,since the Schiff bases are hydrolysable and less stable at lower pH.Under normal physiological conditions(pH 7.4),the release of DOX was slow,and the cumulative release was up to 18.21%within 290 h.However,under the acidic conditions(pH 5.0 and pH 2.03),the release rate of DOX was accelerated,and the cumulative release rates were 41.31%and 86.66%respectively within 290 h.