Preparation And Characterization Of Magnetic Dextran Hydrogel Microspheres

The magnetic hydrogel is a kind of intelligent hydrogel that is magnetically responsive by introducing magnetic nanomaterials into the three-dimensional network structure of hydrogels by physical or chemical methods.magnetic hydrogel was widely used a drug delivery system with magnetic targeting,magnetic hyperthermia and magnetic resonance imaging capabilities.Properties of magnetic hydrogels can be affect strongly by the magnetic nanoparticles used.In order to prepare magnetic particles with small particle size and excellent magnetic properties,the optimum preparation process was investigated by examining the experimental conditions.Dextran has excellent biocompatibility,biodegradability,non-toxicity,a wide range of sources,and it is easily chemically modif ied to give more active derivatives,which can be cross-linked with different ways to have three-dimensional network structure of hydrogel material.In this paper,magnetic hydrogel microparticles were prepared by the inver se microemulsion technique with oxidized dextran as aprecursor,Fe ₃O₄@Dex as a doped magnetic material,and polyethylene imine（PEI）as crosslinker.Finally,5-Aminofluorescein（5-AF）was used as the drug model to study the the drug loading,magnetic and p H-triggered release behavior.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 hydrox ylamine hydrochloride titration.The results showed that aldehyde content on Dex-CHO was 5.97±0.013mmol/g and oxidation degree of dextran was（104.68±0.08）%.Based on the previous study of our group using ethylenediamine as a cross-linking agent,we have explored the optimal concentration of oxidized dext ran and PEI for hydrogel preparations.The results showed that homogeneous hydrogels can be formed with the concentration of Dex-CHO is about 100 mg/m L.（2）The dextran-coated superparamagnetic iron oxides nanoparticles was prepared by chemical co-precipitation method.Based on previous publications,the effects of temperature and amount of dispersant on the properties of magnetic Fe₃O₄ nanoparticles were investigated.The results showed that Fe ₃O₄nanoparticles with ralatively smaller particle size of 21 n m was prepared when the n(Fe³⁺)/n(Fe²⁺)=1.65∶1,reaction time 60 min,p H value of system environment is 11,system reaction temperature is 50℃.,dispersant dextran dosage 0.5 g Magnetic property measurement shows that the resulted Fe ₃O₄ nanoparticle is superparamagnetic with saturation magnetic intensity at 55.8 emu/g Fe.（3）Using 5-aminofluorescein as a drug model,the drug was first connected with oxidized dextran by Schiff’s base structure,magnetic Fe₃O₄@Dex nanoparticles were introduced in a physical doping form,and PEI was used as a cross-linkingagent.The5-aminofluorescein-loadedmagnetichydrogel microspheres were prepared by a reverse microemulsion method.The drug-loading and sustained release in vitro were studied.The results showed that whe n the concentration of 5-aminofluorescein was 1 mg/m L,the highest drug loading rate was 85.88%.The results of sustained release in vitro showed that the magnetic hydrogel microspheres have p H response and magnetic responsiveness as drug carriers.Under simulated human normal physiological conditions（p H=7.4）,the drug release rate is low,and under the same conditions in an external static magnetic field（SMF）environment,the drug release rate is only one third.The drug release rate is high under simu lated tumor tissue environment（p H=5.0）.This indicates that the magnetic hydrogel as a drug carrier can achieve p H and magnetic dual response...