Thermosensitive hydrogels have been studied as feasible needle-avoidance alternative to vaccine delivery. In this work, we report the development of a new thermal-sensitive hydrogel for intranasal vaccine delivery. This delivery system was formulated with a combination of the polymer Gantrez® AN119 and the surfactant Pluronic® F127 (PF127), with a high biocompatibility, biodegradability and immunoadjuvant properties. Shigella flexneri outer membrane vesicles were used as the antigen model. A stable and easy-to-produce thermosensitive hydrogel which allowed the incorporation of the OMV-antigenic complex was successfully synthetized. A rapid gel formation was achieved at body temperature, which prolonged the OMV-antigens residence time in the nasal cavity of BALB/c mice when compared to intranasal delivery of free-OMVs. In addition, the bacterial antigens showed a fast release profile from the hydrogel in vitro, with a peak at 30 min of incubation at 37 °C. Hydrogels appeared to be non-cytotoxic in the human epithelial HeLa cell line and nose epithelium as well, as indicated by the absence of histopathological features. Immunohistochemical studies revealed that after intranasal administration the OMVs reached the nasal associated lymphoid tissue. These results support the use of here described thermosensitive hydrogels as a potential platform for intranasal vaccination.

译文

已经研究了热敏水凝胶作为疫苗递送的可行避免针的替代方法。在这项工作中,我们报告了用于鼻内疫苗递送的新型热敏水凝胶的开发。该输送系统是由聚合物Gantrez的组合配制而成的。®AN119和表面活性剂Pluronic®F127 (PF127),具有较高的生物相容性、生物降解性和免疫佐剂特性。福氏志贺菌外膜囊泡被用作抗原模型。成功合成了一种稳定且易于生产的热敏水凝胶,该凝胶允许掺入OMV抗原复合物。在体温下实现了快速的凝胶形成,与鼻内递送游离OMV相比,延长了OMV抗原在BALB/c小鼠鼻腔中的停留时间。此外,细菌抗原在体外显示出从水凝胶的快速释放曲线,在37 °C孵育30分钟时达到峰值。水凝胶在人上皮HeLa细胞系和鼻子上皮中似乎也是非细胞毒性的,这由缺乏组织病理学特征所表明。免疫组织化学研究表明,鼻内给药后,omv到达鼻相关淋巴组织。这些结果支持使用此处描述的热敏水凝胶作为鼻内疫苗接种的潜在平台。

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