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用于经皮免疫的具有优化针几何形状的溶解微针阵列

Dissolving Microneedle Arrays with Optimized Needle Geometry for Transcutaneous Immunization.

作者信息

Li Yingying, Hu Xia, Dong Zhiyong, Chen Yuanzheng, Zhao Weiman, Wang Yushuai, Zhang Lu, Chen Minglong, Wu Chuanbin, Wang Qingqing

机构信息

Faculty of Pharmacy, Bengbu Medical College, Bengbu, China.

Sun Yat-sen University, Guangzhou, China.

出版信息

Eur J Pharm Sci. 2020 Aug 1;151:105361. doi: 10.1016/j.ejps.2020.105361. Epub 2020 May 16.

Abstract

In this study, the feasibility of transcutaneous immunization using different needle-geometries dissolving microneedle array (DMNA) were investigated as drug carriers for ovalbumin (OVA) preparations. A two-step molding process was used in which needles were loaded with OVA. The microneedles displayed a geometry and dimensions consistent with the main molds. DMNA with different needle-geometries were compared and characterized. Drug loading of the prepared DMNAs reached ~100 μg measured via BCA assay. The stability of OVA in the DMNAs was investigated by SDS-PAGE electrophoresis and showed that the OVA encapsulated in the DMNAs was stable during preparation. The immune responses induced by the DMNAs and hypodermic needle-based injections were compared through in vivo immunoglobulin G (IgG) production assays. OVA-loaded DMNAs also induced stronger immune responses compared to hypodermic needle-based injections. In conclusion, these results suggest that: (1) the needle-morphology of DMNAs influences their mechanical properties, insertion capacity, and dissolution, thus affecting the immune response; (2) Cone-DMNAs are optimal for transcutaneous immunization. These data provide a theoretical basis for the use of transcutaneous immunization of DMNAs for vaccine development.

摘要

在本研究中,研究了使用不同针几何形状的溶解微针阵列(DMNA)作为卵清蛋白(OVA)制剂的药物载体进行经皮免疫的可行性。采用两步成型工艺,将OVA加载到微针中。微针的几何形状和尺寸与主模具一致。对具有不同针几何形状的DMNA进行了比较和表征。通过BCA测定法测得,制备的DMNA的药物负载量达到约100μg。通过SDS-PAGE电泳研究了OVA在DMNA中的稳定性,结果表明,封装在DMNA中的OVA在制备过程中是稳定的。通过体内免疫球蛋白G(IgG)产生试验比较了DMNA和皮下注射诱导的免疫反应。与皮下注射相比,负载OVA的DMNA也诱导了更强的免疫反应。总之,这些结果表明:(1)DMNA的针形态会影响其机械性能、插入能力和溶解性,从而影响免疫反应;(2)锥形DMNA最适合经皮免疫。这些数据为将DMNA用于经皮免疫疫苗开发提供了理论依据。

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