Department of Microbiology and Parasitology, Institute of Tropical Health University of Navarra, 31008 Pamplona, Spain.
Department of Technology and Pharmaceutical Chemistry, University of Navarra, Spain.
Int J Pharm. 2020 Apr 15;579:119154. doi: 10.1016/j.ijpharm.2020.119154. Epub 2020 Feb 17.
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.
温敏水凝胶已被研究作为可行的疫苗接种避针替代物。在这项工作中，我们报告了一种新的用于鼻内疫苗传递的温敏水凝胶的开发。该传递系统由聚合物 Gantrez® AN119 和表面活性剂 Pluronic® F127（PF127）的组合配制而成，具有高生物相容性、可生物降解性和免疫佐剂特性。福氏志贺氏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温敏水凝胶，允许掺入 OMV-抗原复合物。在体温下可迅速形成凝胶，与鼻内给予游离 OMV 相比，延长了 OMV 抗原在 BALB/c 小鼠鼻腔中的停留时间。此外，在体外，细菌抗原从水凝胶中的释放呈快速释放特征，在 37°C 孵育 30 分钟时达到峰值。水凝胶在人上皮 HeLa 细胞系和鼻上皮中似乎没有细胞毒性，因为没有组织病理学特征。免疫组织化学研究表明，鼻内给予 OMV 后，它们到达了鼻相关淋巴组织。这些结果支持使用这里描述的温敏水凝胶作为鼻内疫苗接种的潜在平台。
