Vallhov Helen, Xia Wei, Engqvist Håkan, Scheynius Annika
Department of Clinical Science and Education, Karolinska Institutet, and Sachs' Children and Youth Hospital, Södersjukhuset, SE-118 83 Stockholm, Sweden.
J Mater Chem B. 2018 Nov 14;6(42):6808-6816. doi: 10.1039/c8tb01476k. Epub 2018 Oct 11.
Microneedle-based vaccination into skin has several advantages over vaccination using conventional needles for intramuscular or subcutaneous injections. Microneedle (MN) arrays allow the vaccine to be delivered in a minimally invasive manner and directly into the skin, whereby the skin's superficial immune cells are not by-passed. Additionally, a systemic distribution of the vaccine may be avoided, which implies less side effects and less amount of vaccine needed. For a successful delivery, the needles need to penetrate the stratum corneum and reach the potent network of antigen-presenting dendritic cells (DCs). In this study, we evaluated patches covered with biodegradable ceramic (calcium sulphate) MNs with a tip diameter of approximately 3 μm and with two different lengths (300 and 600 μm) for their ability to penetrate and transfer the model allergen ovalbumin (OVA) into epidermis. MNs with a length of 600 μm (MN-600) and a volume average pore size of 12 ± 1 μm were more efficient in crossing the stratum corneum and to deliver OVA into CD1a DCs residing in the epidermis of human ex vivo skin, in comparison to MNs with a length of 300 μm. Quantitative in vitro release studies showed that approximately 90% of the loaded OVA could be released from MN-600 within 1 h. These findings support the further development of ceramic MNs for transcutaneous immunization.
基于微针的皮肤接种疫苗相较于使用传统针头进行肌内或皮下注射接种疫苗具有多个优势。微针(MN)阵列能使疫苗以微创方式直接递送至皮肤,从而不会绕过皮肤的浅表免疫细胞。此外,可避免疫苗的全身分布,这意味着副作用更少且所需疫苗量更少。为实现成功递送,针头需穿透角质层并抵达强大的抗原呈递树突状细胞(DC)网络。在本研究中,我们评估了覆盖有可生物降解陶瓷(硫酸钙)微针的贴片,其针尖直径约为3μm,有两种不同长度(300和600μm),评估其穿透并将模型变应原卵清蛋白(OVA)转移至表皮的能力。与长度为300μm的微针相比,长度为600μm(MN - 600)且体积平均孔径为12±1μm的微针在穿过角质层并将OVA递送至人离体皮肤表皮中的CD1a DC方面效率更高。定量体外释放研究表明,约90%负载的OVA可在1小时内从MN - 600中释放。这些发现支持了用于经皮免疫的陶瓷微针的进一步开发。