Zhou Shaobing, Deng Xianmo, He Shuiying, Li Xiaohong, Jia Wenxiang, Wei Dapeng, Zhang Zairong, Ma Jihui
Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, P. R. China.
J Pharm Pharmacol. 2002 Sep;54(9):1287-92. doi: 10.1211/002235702320402143.
In this work, a new microsphere delivery system comprising calcium alginate microcores surrounded by a biodegradable poly-DL-lactide-poly(ethylene glycol) (PELA) coat was designed to improve the loading efficiency and stability of peptide drugs. Recombinant interferon (IFN)-alpha-2a, used as a model peptide drug, was efficiently entrapped within the alginate microcores using a high-speed stirrer and then microencapsulated into PELA copolymer using a water-in-oil-in-water solvent extraction method. Microspheres were characterized in terms of morphology, size and distribution, encapsulation efficiency, IFN biological activity retention and in-vitro peptide release. The IFN potency test showed that IFN entrapped in the core-coated microspheres could retain its biological activity during the encapsulation and release procedure. The release profiles were determined by the measurement of peptide presenting in the release medium at various intervals. The IFN potency, calculated by the Wish cells/vesicular stomatitis virus system, was used to determine IFN biological activity. The results showed that the core-coated microspheres could stabilize IFN in the PELA matrix. We compared the new deliverysystem with conventional microsphere delivery systems based on biodegradable poly-DL-lactide and poly-DL-lactide-poly(ethylene glycol). The core-coated microspheres had the highest amount of entrapment, encapsulation efficiency and biological activity retention. The extent of burst release (14%) from the core-coated microspheres in the initial protein release was much lower than the 31% burst release from the conventional microspheres. In conclusion, this work presents a new approach for water-soluble macromolecular drugs delivery (e.g. protein, peptide drugs, vaccines).
在本研究中，设计了一种新型微球递送系统，该系统由海藻酸钙微核和可生物降解的聚-DL-丙交酯-聚（乙二醇）（PELA）包衣组成，旨在提高肽类药物的负载效率和稳定性。以重组干扰素（IFN）-α-2a作为模型肽类药物，使用高速搅拌器将其有效地包封在海藻酸盐微核内，然后采用水包油包水溶剂萃取法将其微囊化到PELA共聚物中。对微球进行了形态、大小和分布、包封效率、IFN生物活性保留以及体外肽释放等方面的表征。IFN效价测试表明，包封在核-壳微球中的IFN在包封和释放过程中能够保留其生物活性。通过在不同时间间隔测量释放介质中存在的肽来确定释放曲线。采用Wish细胞/水泡性口炎病毒系统计算的IFN效价用于确定IFN生物活性。结果表明，核-壳微球能够使IFN在PELA基质中稳定存在。我们将这种新型递送系统与基于可生物降解聚-DL-丙交酯和聚-DL-丙交酯-聚（乙二醇）的传统微球递送系统进行了比较。核-壳微球具有最高的包封量、包封效率和生物活性保留率。核-壳微球在初始蛋白质释放时的突释程度（14%）远低于传统微球的31%突释率。总之，本研究为水溶性大分子药物（如蛋白质、肽类药物、疫苗）的递送提供了一种新方法。
