载胰岛素壳聚糖-果胶微球的制备及性能研究

Preparation and characterization of insulin loading chitosan-pectin microspheres

目的以壳聚糖与果胶为载体,三聚磷酸钠、氯化钙为固化剂,制备载胰岛素的壳聚糖-果胶微球,并对微球的基本性质、载药性能及成型机制进行考察。方法采用离子移变胶凝法制备载胰岛素的壳聚糖-果胶微球,采用高效液相色谱法测定包封率,以微球形态、粒径、包封率作为考察指标,进行处方工艺的单因素筛选。用差示扫描量热法与傅里叶变换红外光谱法对微球的成型机制进行初步探讨。初步考察了载胰岛素壳聚糖-果胶微球的体外释药行为。结果胰岛素在0.8～60μg.mL-1内呈现良好的线性,相关系数r=0.999 8。所制备的微球形态圆整,平均粒径为(38.06±3.89)μm,包封率为(44.06±1.63)%。由DSC图谱推断,形成微球时,壳聚糖与果胶之间发生了相互作用。微球的FTIR图谱中未出现新的特征峰,推断在形成微球时,壳聚糖、果胶、胰岛素之间未发生化学反应。初步考察了载胰岛素壳聚糖-果胶微球体外释药呈现明显的缓释作用。结论本法制备工艺简单,重复性好,所制备的胰岛素微球外观圆整,粒径大小分布较均匀,具有明显缓释作用,但包封率不够理想,尚需进一步提高。

Objective To prepare insulin（INS） microspheres（MSs） with chitosan（CTS） and pectin（PEC） as carrier materials,sodium tripolyphosphate（STPP） and CaCl2 as solidification agents,and to investigate the basic properties,drug loading capacity and formation mechanism of microspheres.Methods The insulin loading chitosan-pectin microspheres（INS-CTSPEC MSs） were prepared by ionotropic gelation method.The high performance liquid chromatography（HPLC） was used to measure drug entrapment efficiency（EE）.The shape,particle size and EE of MS were used to screen formulation and process by single-factor experiment.The formation mechanism of MS was preliminarily discussed by differential scanning calorimetry（DSC） and fourier transform infrared spectrometry（FTIR）.The drug release behavior of INS-CTS-PEC MS was investigated.Results Insulin showed a good linearity at the concentration range of 0.8-60 μg.mL-1（r = 0.999 8）.The INS-CTS-PEC MSs of（38.06±3.89） μm were achieved with good sphericity and the EE of（44.06±1.63）%.The DSC spectra indicated an interaction between chitosan and pectin when forming microspheres.The FTIR spectrum of microsphere showed no new characteristic peak,which indicated no chemical reaction between chitosan,pectin and insulin.The INSCTS-PEC MSs de,pmstrated a typical sustained release pattern.Conclusion The INS-CTS-PEC MSs are prepared by simple process and of perfect spheric appearance and narrow size distribution with good reproducibility.The microspheres possess good prolonged release behavior in vitro.However,the EE is not satisfactory enough and needs further enhancement.