Siddhapura Krupa, Harde Harshad, Jain Sanyog
Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab, India.
Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab, India.
Nanomedicine. 2016 Jan;12(1):213-22. doi: 10.1016/j.nano.2015.10.009. Epub 2015 Nov 10.
The present study investigated potential of tetanus toxoid loaded chitosan nanoparticles (TT-Ch-NPs) following bare topical and microneedles assisted immunization. The TT-Ch-NPs were prepared by ionotropic gelation method using poly(sodium-4-styrene sulfonate) (PSS) as crosslinking agent which exhibited ~208 nm size and ~99% entrapment efficiency. The manufacturing process did not have any detrimental effect on integrity and conformation of antigen. The in vitro analysis demonstrated higher skin penetration following microneedles assisted immunization. In vivo immunization studies exhibited that TT-Ch-NPs delivered through microneedles induced comparable IgG and IgG1 titer, yet higher IgG2a titer than commercial TT vaccine. Similarly, microneedles assisted administration of TT-Ch-NPs generated higher Th1 cytokines, albeit no significant alteration in Th2 cytokines levels than commercial TT vaccine. In conclusion, microneedles assisted administration of TT-Ch-NPs especially via hollow microneedles (HMN) could be considered as best preferred route for immunization due to induction of more balanced Th1/Th2 biased immune response. From the Clinical Editor: The use of skin as a route for vaccination has been a clinically important topic for some time. In this article, the authors investigated the efficacy of both solid microneedles and hollow microneedles as methods for topical delivery of tetanus toixoid. The positive finding in the experiments could provide a better method for vaccination in the clinical setting in the future.
本研究调查了破伤风类毒素负载壳聚糖纳米颗粒（TT-Ch-NPs）在单纯局部给药和微针辅助免疫后的潜力。采用聚（4-苯乙烯磺酸钠）（PSS）作为交联剂，通过离子凝胶法制备了TT-Ch-NPs，其粒径约为208 nm，包封率约为99%。制备过程对抗原的完整性和构象没有任何不利影响。体外分析表明，微针辅助免疫后皮肤渗透率更高。体内免疫研究表明，通过微针递送的TT-Ch-NPs诱导的IgG和IgG1滴度与市售TT疫苗相当，但IgG2a滴度高于市售TT疫苗。同样，微针辅助给药的TT-Ch-NPs产生的Th1细胞因子更高，尽管与市售TT疫苗相比，Th2细胞因子水平没有显著变化。总之，微针辅助给药的TT-Ch-NPs，尤其是通过中空微针（HMN）给药，由于能诱导更平衡的Th1/Th2偏向性免疫反应，可被认为是最佳的免疫途径。临床编辑评论：将皮肤作为疫苗接种途径在临床上一直是一个重要课题。在本文中，作者研究了固体微针和中空微针作为破伤风类毒素局部递送方法的效果。实验中的阳性结果可为未来临床环境中的疫苗接种提供更好的方法。
