口服胸腺肽肠溶微球的制备及其体内外评价

 目的制备胸腺肽肠溶微球,并对其体外释药特性及调节免疫的体内活性进行评价。方法以聚丙烯酸树脂Ⅱ号为载体材料,用改良的O/O液中干燥法制备胸腺肽肠溶微球。考察了载药量、聚合物浓度对包封率和微球体外释药特性的影响,并进一步探讨口服胸腺肽微球对氢化可的松免疫抑制小鼠免疫功能的影响。结果实验表明,随着载药量的增加,包封率呈下降趋势;聚合物溶液浓度提高会增加微球的包封率。通过优化制备工艺参数,药物包封率可达89.7%。胸腺肽微球在体外释药有明显突释,提高聚合物浓度,降低载药量可以减少体外突释。氢化可的松免疫抑制小鼠经口服胸腺肽微球后可以提高小鼠淋巴细胞玫瑰花结形成率,证明所制备的胸腺肽微球具有免疫调节活性。结论用改良的O/O液中干燥法制备胸腺肽肠溶微球,通过调节制备工艺参数,可以得到高包封率的微球。动物实验表明,胸腺肽肠溶微球口服后具有调节和增强免疫的作用。

Preparation and Evaluation of Thymosin-Loaded Enteric Microspheres in vivo and in vitro

OBJECTIVE To prepare enteric microspheres containing thymosin, and evaluate its in vitro release profiles and in vivo bioactivity. METHODS Thymosin-loaded enteric microspheres were prepared by modified oil-in-oil(O/O)emulsion solvent evaporation method, acrylic acid resin Ⅱ was used as carrier material. The effects of process parameters, such as initial drug feed and polymer concentration,on drug encapsulation efficiency and in vitro release profiles were investigated.After oral administration, the effect of thymosin-loaded microparticles on the immunity of hydrocortisone induced immunosuppressed mice was also examined.RESULTS Increase of initial drug feed led to a decrease in entrapment efficiency, while increasing polymer concentration resulted in an increase in drug entrapment efficiency.After adoptingoptimized preparation formulation, thymosin entrapment efficiency of 89.7% was achieved. Thymosin release from microspheres exhibited significant burst release, while increase in polymer concentration and reduction in drug loading decreased burst release. Orally administrated microspheres enhanced the E-rosette formation rate of lymphocyte in immunosuppressed mice induced by hydrocortisone.Thymosin-loaded microspheres had immuno-regulativity.CONCLUSION Modified O/O emulsion solvent evaporation method is adopted to prepare thymosin containing enteric microspheres. By optimizing preparation parameters, microspheres with higher entrapment efficiency are produced. The bioactivity of thymosin is not influenced during microsphere preparation process, and it has the ability to regulate and enhance immunity.