Bussio Juan I, Molina-Perea Carla, González-Aramundiz José Vicente
Departamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago 7820436, Chile.
Centro de Investigación en Nanotecnología y Materiales Avanzados "CIEN-UC", Pontificia Universidad Católica de Chile, Santiago 7820436, Chile.
Nanomaterials (Basel). 2018 Aug 26;8(9):659. doi: 10.3390/nano8090659.
Transcutaneous vaccination has several advantages including having a noninvasive route and needle-free administration; nonetheless developing an effective transdermal formulation has not been an easy task because skin physiology, particularly the stratum corneum, does not allow antigen penetration. Size is a crucial parameter for successful active molecule administration through the skin. Here we report a new core-shell structure rationally developed for transcutaneous antigen delivery. The resulting multifunctional carrier has an oily core with immune adjuvant properties and a polymeric corona made of chitosan. This system has a size of around 100 nm and a positive zeta potential. The new formulation is stable in storage and physiological conditions. Ovalbumin (OVA) was used as the antigen model and the developed nanocapsules show high association efficiency (75%). Chitosan nanocapsules have high interaction with the immune system which was demonstrated by complement activation and also did not affect cell viability in the macrophage cell line. Finally, ex vivo studies using a pig skin model show that OVA associated to the chitosan nanocapsules developed in this study penetrated and were retained better than OVA in solution. Thus, the physicochemical properties and their adequate characteristics make this carrier an excellent platform for transcutaneous antigen delivery.
经皮接种疫苗具有多种优势，包括采用非侵入性途径且无需注射；然而，开发一种有效的透皮制剂并非易事，因为皮肤生理结构，尤其是角质层，不允许抗原穿透。尺寸是通过皮肤成功递送活性分子的关键参数。在此，我们报告一种为经皮递送抗原而合理开发的新型核壳结构。所得的多功能载体具有具有免疫佐剂特性的油性核心以及由壳聚糖制成的聚合物冠层。该系统尺寸约为100纳米，且具有正的zeta电位。新制剂在储存和生理条件下均稳定。卵清蛋白（OVA）用作抗原模型，所开发的纳米胶囊显示出高结合效率（75%）。壳聚糖纳米胶囊与免疫系统具有高度相互作用，这通过补体激活得以证明，并且对巨噬细胞系中的细胞活力没有影响。最后，使用猪皮肤模型进行的体外研究表明，与本研究中开发的壳聚糖纳米胶囊结合的OVA比溶液中的OVA穿透性更好且保留性更佳。因此，其物理化学性质及其适当特性使该载体成为经皮抗原递送的优良平台。
