Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Shameerpet, Hyderabad, Telangana State, 500078, India.
AAPS PharmSciTech. 2019 Jul 22;20(7):257. doi: 10.1208/s12249-019-1471-3.
Transcutaneous immunization using a microneedle device presents a promising alternative to syringe-based injection of vaccines. The aim of this study was to investigate the effective immune response elicited after application of tetanus toxoid antigen-loaded dissolvable microneedles (TT-MN) in mice model. Dissolvable microneedles were prepared using 20% w/v of polyvinyl alcohol and polyvinyl pyrrolidone polymer mixture by micromolding technique. TT-MN were prepared by addition of tetanus toxoid to polymer mixture before casting microneedles. TT-MN were characterized using texture analyzer, stereomicroscope, and scanning electron microscope. Tetanus toxoid loading was found to be 77 ± 2 μg per microneedle array. Confocal microscopic analysis showed that the microneedles penetrated to a depth of 130 μm inside mouse skin. Complete dissolution of microneedles was achieved within 1 h after insertion in skin. Immunization studies in Swiss albino mice demonstrated significantly (p < 0.001) greater IgG, IgG, and IgG antibody titers for TT-MN and intramuscular injection groups compared with naïve control. Splenocyte proliferation assay confirmed effective re-stimulation on exposure to tetanus toxoid in microneedle treatment groups. Taken together, TT-MN can be developed as minimally invasive system for transcutaneous delivery of tetanus toxoid antigen.
经皮免疫使用微针装置为基于注射器的疫苗接种提供了一种很有前途的替代方法。本研究的目的是研究破伤风类毒素抗原负载可溶解微针（TT-MN）在小鼠模型中应用后引起的有效免疫反应。可溶解微针是通过微成型技术用 20% w/v 的聚乙烯醇和聚乙烯吡咯烷酮聚合物混合物制备的。在铸造微针之前，将破伤风类毒素添加到聚合物混合物中制备 TT-MN。使用纹理分析仪、立体显微镜和扫描电子显微镜对 TT-MN 进行了表征。TT-MN 的破伤风类毒素载量为每根微针阵列 77±2μg。共焦显微镜分析显示，微针在小鼠皮肤内穿透深度为 130μm。微针插入皮肤后 1 小时内完全溶解。在瑞士白化病小鼠中的免疫研究表明，与空白对照组相比，TT-MN 和肌肉注射组的 IgG、IgG 和 IgG 抗体滴度显著（p<0.001）更高。脾细胞增殖试验证实了在微针治疗组中暴露于破伤风类毒素时的有效再刺激。综上所述，TT-MN 可以开发为破伤风类毒素抗原经皮递药的微创系统。
