PDF(Pubmed)
Abstract：
The oral mucosa is an attractive site for immunization due to its accessibility and ability to elicit local and systemic immune responses. However, evaluating oral mucosal immunogenicity has proven challenging due to the physical barriers and immunological complexity of the oral mucosa. Microneedles can overcome these physical barriers, but previous work has been limited in the scope of microneedle delivery site, geometry, and release kinetics, all of which are expected to affect physiological responses. Here, we develop integrated fiber microneedle devices, an oral dosage form with tunable geometries and material configurations capable of both burst and sustained release to controlled depths in the oral mucosa. Integrated fiber microneedles administered to either the buccal or sublingual mucosa result in seroconversion and antigen-specific interferon-γ secretion in splenocytes. The dynamics and magnitude of the resulting immune response can be modulated by tuning microneedle release kinetics. Optimal microneedle geometry is site-specific, with longer microneedles eliciting greater immunogenicity in the buccal mucosa, and shorter microneedles eliciting greater immunogenicity in the sublingual mucosa. The Th1/Th2 phenotype of the resulting immune response is also dependent on integrated fiber microneedle length. Together, these results establish integrated fiber microneedles as a multifunctional delivery system for the oral mucosa and motivate further exploration using tunable delivery systems to better understand oral mucosal immunity.
摘要：
口腔粘膜由于其可接近性和引发局部和全身免疫应答的能力而成为免疫的有吸引力的部位。然而,由于口腔粘膜的物理屏障和免疫复杂性，评估口腔粘膜免疫原性已被证明具有挑战性。微针可以克服这些物理障碍，但是以前的工作仅限于微针递送部位的范围，几何图形,和释放动力学，所有这些都会影响生理反应。这里,我们开发了集成的纤维微针装置，一种具有可调几何形状和材料构型的口服剂型，能够在口腔粘膜中爆发和持续释放到受控深度。施用至颊粘膜或舌下粘膜的整合纤维微针导致脾细胞中的血清转化和抗原特异性干扰素-γ分泌。所产生的免疫应答的动力学和量级可以通过调节微针释放动力学来调节。最佳微针几何形状是位点特异性的，较长的微针在颊粘膜中引起更大的免疫原性，和较短的微针在舌下粘膜中引起更大的免疫原性。所产生的免疫应答的Th1/Th2表型也依赖于整合的纤维微针长度。一起,这些结果建立了集成纤维微针作为口腔黏膜的多功能递送系统，并激发了使用可调递送系统的进一步探索，以更好地了解口腔黏膜免疫。
