Project for Vaccine and Immune Regulation, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; Laboratory of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Department of Dermatology, Nara Medical University, 840 Shin-cho, Kashihara, Nara 634-8522, Japan; Department of Dermatology,Course of Integrated Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Int J Pharm. 2017 Oct 30;532(1):374-383. doi: 10.1016/j.ijpharm.2017.08.110. Epub 2017 Aug 30.
Microneedle (MN) patches have great potential as transcutaneous vaccine delivery devices because MNs can effectively deliver vaccine antigen into the skin through the micropores formed in the stratum corneum by low-invasive and painless skin puncturing. This study aims to develop novel double-decker MN patches which have not only high safety and efficacy but also broad applicability to various vaccine antigens. We developed two types of MN patches (PGA-MN and Nylon-MN) that are made from polyglycolic acid and Nylon-6. In pre-clinical studies, both MN patches could demonstrably deliver antigens into resected human dermal tissue, prolong antigen deposition and increase antigen-specific IgG levels after vaccination compared with conventional injections. We demonstrated both MN patches could be safely applied to human skin because no broken MNs or significant skin irritation were observed after applications in the clinical research. PGA-MN was suggested to be superior to Nylon-MN regarding human skin puncturability based on measurements of transepidermal water loss and needle failure force. A high content of tetravalent influenza hemagglutinin antigens loaded on PGA-MN could stably maintain HA titers at 35°C for 1year. Overall, double-decker MN patches can reliably and safely puncture human skin and are promising as effective transcutaneous vaccine delivery devices.
微针 (MN) 贴剂作为经皮疫苗传递装置具有很大的潜力，因为 MN 通过微创和无痛的皮肤穿刺在角质层中形成的微孔，可以有效地将疫苗抗原递送至皮肤中。本研究旨在开发新型双层 MN 贴剂，其不仅具有高安全性和有效性，而且还具有广泛适用于各种疫苗抗原的特性。我们开发了两种 MN 贴剂（PGA-MN 和 Nylon-MN），它们由聚乙醇酸和尼龙-6 制成。在临床前研究中，与传统注射相比，这两种 MN 贴剂都能明显地将抗原递送至切除的人体真皮组织中，延长抗原沉积并增加疫苗接种后的抗原特异性 IgG 水平。我们证明了这两种 MN 贴剂都可以安全地应用于人体皮肤，因为在临床研究中应用后没有观察到 MN 断裂或明显的皮肤刺激。PGA-MN 在人体皮肤穿刺能力方面优于 Nylon-MN，这是基于经皮水分流失和针失效力的测量。高含量的四价流感血凝素抗原负载在 PGA-MN 上可以在 35°C 下稳定地保持 HA 效价 1 年。总的来说，双层 MN 贴剂可以可靠且安全地穿刺人体皮肤，是有前途的有效经皮疫苗传递装置。
