Graduate Program on Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio Grande do Norte, Rua General Gustavo Cordeiro de Farias, S/N, Petrópolis, Natal 59012-570, Brazil.
Graduate Program on Biochemistry, Bioscience Center, University Campus, Federal University of Rio Grande do Norte, Avenida Senador Salgado Filho, 3000, Lagoa Nova, 59072-970 Natal, Brazil.
Int J Biol Macromol. 2018 Dec;120(Pt B):1917-1924. doi: 10.1016/j.ijbiomac.2018.09.203. Epub 2018 Oct 1.
Snakebite envenoming is a tropical disease neglected worldwide. In Brazil, the Crotalus durissus cascavella (CDC) snake belongs to a genus with venom of highest lethality. A search for new immunoadjuvants aimed to expand the therapeutic alternatives to improve vaccines and antivenom. This approach proposed to produce small and narrow-sized cationic CDC venom-loaded chitosan nanoparticles (CHNP) able to induce antibody response against the CDC venom. The ionic gelation method induced the formation of stable and slightly smooth spherical nanoparticles (<160 nm) with protein loading efficiency superior to 90%. The interactions between venom proteins and CHNP assessed using FT-IR spectroscopy corroborated with the in vitro release behavior of proteins from nanoparticles. Finally, the immunization animal model using BALB/c mice demonstrated the higher effectiveness of CDC venom-loaded CHNP compared to aluminum hydroxide, a conventional immunoadjuvant. Thus, CHNPs loaded with CDC venom exhibited a promising biotechnological approach to immunotherapy.
蛇伤中毒是一种被全世界忽视的热带疾病。在巴西,响尾蛇(CDC)属于一种毒液致死率最高的蛇类。人们一直在寻找新的免疫佐剂,以期扩大治疗选择,改善疫苗和抗蛇毒血清的效果。本研究提出制备小而窄尺寸的阳离子化响尾蛇毒液壳聚糖纳米颗粒(CHNP),以诱导针对响尾蛇毒液的抗体反应。离子凝胶法诱导形成稳定的、略带光滑的球形纳米颗粒(<160nm),蛋白载药效率超过 90%。使用傅里叶变换红外光谱(FT-IR)评估毒液蛋白与 CHNP 的相互作用,与蛋白从纳米颗粒中的体外释放行为一致。最后,使用 BALB/c 小鼠的免疫动物模型表明,与传统免疫佐剂氢氧化铝相比,载有响尾蛇毒液的 CHNP 具有更高的有效性。因此,载有响尾蛇毒液的 CHNP 为免疫治疗提供了一种有前途的生物技术方法。