Rattanapak Teerawan, Birchall James C, Young Katherine, Kubo Atsuko, Fujimori Sayumi, Ishii Masaru, Hook Sarah
School of Pharmacy, University of Otago, Dunedin, New Zealand.
School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, United Kingdom.
PLoS One. 2014 Feb 24;9(2):e89503. doi: 10.1371/journal.pone.0089503. eCollection 2014.
Delivery of vaccines into the skin provides many advantages over traditional parenteral vaccination and is a promising approach due to the abundance of antigen presenting cells (APC) residing in the skin including Langerhans cells (LC) and dermal dendritic cells (DDC). However, the main obstacle for transcutaneous immunization (TCI) is the effective delivery of the vaccine through the stratum corneum (SC) barrier to the APC in the deeper skin layers. This study therefore utilized microneedles (MN) and a lipid-based colloidal delivery system (cubosomes) as a synergistic approach for the delivery of vaccines to APC in the skin. The process of vaccine uptake and recruitment by specific types of skin APC was investigated in real-time over 4 hours in B6.Cg-Tg (Itgax-EYFP) 1 Mnz/J mice by two-photon microscopy. Incorporation of the vaccine into a particulate delivery system and the use of MN preferentially increased vaccine antigen uptake by a highly motile subpopulation of skin APC known as CD207⁺ DC. No uptake of antigen or any response to immunisation by LC could be detected.
与传统的肠胃外疫苗接种相比,将疫苗递送至皮肤具有诸多优势,并且由于皮肤中存在大量抗原呈递细胞(APC),包括朗格汉斯细胞(LC)和真皮树突状细胞(DDC),这是一种很有前景的方法。然而,经皮免疫(TCI)的主要障碍是如何使疫苗有效穿过角质层(SC)屏障,到达更深层皮肤中的APC。因此,本研究采用微针(MN)和基于脂质的胶体递送系统(立方液晶纳米粒)作为一种协同方法,将疫苗递送至皮肤中的APC。通过双光子显微镜,在4小时内实时研究了B6.Cg-Tg (Itgax-EYFP) 1 Mnz/J小鼠中特定类型皮肤APC摄取和募集疫苗的过程。将疫苗掺入颗粒递送系统并使用MN,优先增加了一种高迁移性皮肤APC亚群(称为CD207⁺ DC)对疫苗抗原的摄取。未检测到LC摄取抗原或对免疫有任何反应。