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一种生物技术免疫疗法:从可生物降解纳米颗粒中生产的抗响尾蛇属蛇毒抗血清。

A biotechnological approach to immunotherapy: Antivenom against Crotalus durissus cascavella snake venom produced from biodegradable nanoparticles.

机构信息

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.

出版信息

Int J Biol Macromol. 2018 Dec;120(Pt B):1917-1924. doi: 10.1016/j.ijbiomac.2018.09.203. Epub 2018 Oct 1.

Abstract

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.

摘要

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。

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