Synthesis And Drug-release Properties Of β-CYCLODEXTRIN/N-ISOPROPYLACRYLAMIDE Microspheres

A pH and temperature-sensitive hydrogel microspheres was synthesized withβ-cyclodextrin(β-CD),N-isopropylacrylamide(NIPAAm) and succinic anhydride(SA) as major materials,and its drug-releasing properties were investigated.Firstly, the poly(β-CD) microspheres were synthesized by inverse emulsion polymerization,and the poly(MAH-β-CD) microspheres were obtained by modification of poly(β-CD) with maleic anhydride(MAH).The effects on the particle size and monodispersity of poly(β-CD) microspheres were discussed of stirring type, material proportioning, emulsifier ratio, emulsifier content, reaction temperature, polymerization time and stirring rate.The poly(β-CD) microspheres were modified at the different mass ratio,reaction temperature and time. The poly(β-CD) and poly(MAH-β-CD) microspheres were observed and characterized through biomicroscopy,scanning electron microscope(SEM) and infrared spectroscopy. The results showed that poly(β-CD) microspheres got round surface,better spherical degree,suitable particle size of 100~180μm and preferable dispersities,which were modified under the stirring of about 300r/min,the molar ratio of epichlorohydrin(EPI) andβ-CD being 15:1, the emulsifier dosage 1g,the mass ratio of SP-80and TW-20 being 3:1, 60℃of reaction temperature and 8h of reaction time.The optimum modified conditions were that the mass ratio of MAH and poly(β-CD) microspheres was 3:5,80℃of reaction temperature and 10h of reaction time.The carboxyl group and C=C bonds were ascertained in poly(MAH-β-CD) microspheres through infrared spectrum.Secondly,the pH and temperature sensitive poly(β-CD/NIPAAm-SA) microspheres were prepared by graft copolymerization onto the poly(β-CD) microspheres with NIPAAm and acrylamide(AAm),and the pH-sensitive blocking group(-COOH) leading in microspheres by the reaction of -OH groups in the poly(β-CD/NIPAAm) microspheres with succinic anhydride(SA). The influences of the dosages of NIPAAm, Cerium ammonium nitrate(CAN) and SA on the poly(β-CD/NIPAAm-SA) microspheres were studied,and the pH and temperature sensitivities of the poly(β-CD/NIPAAm-SA) microspheres were researched by the swelling experiments.SEM showed that the poly(β-CD/NIPAAm-SA) microspheres had favorable spherical degree and grain size of 200~300μm.And the swelling results indicated that the swelling rate was decreased with temperature raising and increased with pH value improving,and the volume of phase transition was changed suddenly on the temperature of about 27℃and 38℃,and the pH values of about 1.4 and 7.4.It revealed the poly(β-CD/NIPAAm-SA) microspheres were pH and temperature responsive.Finally, the controlled release behavior of the poly(β-CD/NIPAAm-SA) microspheres was researched using sodium salicylate as a model medicine.The kinetics euuations were fitting of the relations between cumulative release rate and times at the different pH values and temperature.The results showed that the drug releasing rate were quickened with temperature and pH value improving.Therefore,a new drug-controlled delivery system could be established according to the adjusting and controlling function of the poly(β-CD/NIPAAm-SA) microspheres according to the changes of body temperature and pH values in stomach and intestine.