Preparation And Drug Release Properties In Vitro Of Thermo-/pH-sensitive Magnetic β-cyclodextrin Microspheres

Drug delivery carrier plays an important role in improving the efficacy of drugs andreducing the damage to the body. After drugs enter the body via certain administration, how toreduce the loss of drugs before reaching the target sites, reduce the damage to normal tissues,avoid ‘peak-valley’ fluctuations of drug concentration while extending the drug efficacy andincreasing the utilization rate of drugs, is a significant research direction of drug delivery field.Smart polymer materials with environmental sensitivity and magnetic orientation areimportant carriers in bio-pharmaceutical industry, have extensive application prospects in thefield of drug controlled release, especially in targeted treatment of cancer.β-cyclodextrin (β-CD), a kind of molecule with special inclusion feature was taken asmonomer, sodium citrate modified Fe3O4nanoparticles were added to the raw materials, usingepichlorohydrin (EPI) as a crosslinking agent, kerosene as the oil phase, magnetic β-CDmicrospheres were prepared by inverse emulsion polymerization. Then thermo-/pH-sensitivemagnetic β-CD microspheres were synthesized by grafting pH-sensitive molecules succinicanhydride(SA) and temperature-sensitive molecules N-isopropyl acrylamide(NIPAAm) on themicrospheres.The morphology and structure of the products were characterized by FT-IR,XRD, laser particle size analyzer, VSM, SEM and other analytical testing methods.Temperature and pH sensitivity of the microspheres were studied using swelling ratio asparameter, the drug-loading and in vitro drug release properties of the microspheres wereresearched using a hydrophobic anti-cancer drug as a model.In the procedure of magnetic β-CD microspheres preparation, by researching theexperimental conditions it was found that when the molar ratio of EPI to β-CD was16:1,volume ratio of kerosene to water was4:1, the amount of emulsifier was1.6g (in which themass ratio of Span-80to Tween-20was3:1), stirring speed was800r/min, the reaction wasconducted at70℃for8h, the produced microspheres had relatively smaller particlesize anduniform distribution, the median particle diameter was98.31μm and distribution span was1.36. The microspheres were round and smooth, the highest content of Fe3O4was31.6%. Inthe process of grafting reaction proceeded in DMF, when the mass ratio of SA to magnetic β-CD microspheres was0.75:1, the reaction temperature was80℃and reaction time was12h,the obtained microspheres had a maximum SA grafting ratio of19.5%. In the graftingNIPAAm stage, the optimal reaction condition was determined through optimization: whenthe amount of pH-sensitive magnetic β-CD microspheres was1.0g, mass ratio of NIPAAm tomicrospheres was5:1, initiator CAN was0.2g, the reaction temperature was30℃andreaction time was24h. Under which condition the prepared thermo-/pH-sensitive magneticβ-CD microspheres had the highest NIPAAm graft ratio of44.5%, Fe3O4content of10.1%,and saturation magnetization of5.96emu·g-1.The swelling ratio of the synthesized thermo-/pH-sensitive magnetic β-CD microspherespresented characteristics as follows: the swelling ratio reduced with the decrease of pH andrised as the temperature fell in a certain range. The results of drug load and in vitro releaseexperiments used ftorafur (1-(tetrahydro-2-furyl)-5-fluoro-2,4(1H,3H)-pyrimidinedione) as amodel indicated that the maximum drug-loading rate of the microspheres was3.68%, thedrug-loading microspheres presented excellent drug controlled release properities at arelatively higher temperature and an acid environment, and the sustained release time wasbeyond12h.