PLA/MSM缓释微球的制备及生物活性

Preparation of Controlled-release PLA Microspheres Loading Methylsulfonylmethane and Its Biological Activity

采用膜乳化-液中干燥法制备出担载二甲基砜(MSM)的聚乳酸(PLA)微球(PLA/MSM),并研究了膜孔径、搅拌转速和MSM浓度对载药微球形貌、尺寸、载药量、体外释放及细胞活性的影响;采用场发射环境扫描电子显微镜(ESEM)观察微球形貌、尺寸及分布,用等离子体发射光谱(ICP-AES)法检测PLA/MSM微球载药量、包封率及体外释放,采用ESEM观察微球内部结构,并通过体外细胞培养和噻唑蓝(MTT)法检测MC-3T3-E1细胞的增殖能力.研究结果表明,膜乳化法制备的载药微球规整,呈典型的圆球状,表面光滑,内部有多孔结构.当膜孔径为5.1μm且搅拌转速为500 r/min时,PLA/MSM微球大小更为均一;当体系中MSM质量分数为8.6%时,载药量可达到77.43%.随着膜孔径减小及药物浓度的增加,体外释放速率加快,但初期均无明显的突释现象,约10 d后累积释放量达到89.2%.细胞实验结果显示,在膜孔径为5.1μm且MSM质量分数为8.6%的条件下,制备的载药微球在细胞培养7 d时表现出明显的促增殖作用.

Polylactic acid （PLA） microspheres carrying methylsulfonylmethane （MSM） were prepared by membrane emulsification. The effects of membrane pore size, stirring speed and MSM concentration on micro- spheres morphology, size, drug loading and in vitro release, as well as cell biological activity were studied using environmental scanning electron microscope （ESEM） , inductively coupled plasma atomic emission spec- trometer（ ICP-AES）, in vitro culture of MC3T3-E1 cell and 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyhe- trazolium bromide （MTI＇） method. The study will provide references for the study of the long-acting release agent of MSM. The results showed that the drug-loaded microspheres prepared with membrane emulsification were typical spherical with smooth surface and the internal porous structure. The size and morphology of the microspheres could be affected by membrane pore size, stirring speed and MSM concentration. The drug- loaded microspheres prepared with the membrane pore size of 5.1 p^m and a stirring speed of 500 r/min were more uniform in size than others. When the mass fraction of MSM solution was 8.6%, the drug loading of mi- crospheres could be up to 77.43%. The in vitro release rate of MSM could be sped up when the membrane pore size was reduced and the MSM concentration was increased, but the initial burst release for all samples was not obvious, and it reached up to 89.2% after 10 d. The cell experiments showed that cell proliferation of MC3T3-E1 was improved at 7 d cell culture using MSM-loaded microspheres with the membrane pore size of 5.1 μm and MSM mass fraction of 8.6%. The research indicates that the PLA/MSM drug-loaded micro- spheres has good controlled release characteristics and biological activity, which can be used as a long-acting release formulation of MSM for the treatment of osteoarthritis and application in bone and cartilage tissue engi- neering.