The University of Queensland, Delivery of Drugs and Genes Group (D2G2), The Australian Institute for Bioengineering and Nanotechnology, St Lucia, QLD 4072, Australia.
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Queensland, Australia.
Sci Rep. 2016 Jun 2;6:27217. doi: 10.1038/srep27217.
Micro-device use for vaccination has grown in the past decade, with the promise of ease-of-use, painless application, stable solid formulations and greater immune response generation. However, the designs of the highly immunogenic devices (e.g. the gene gun, Nanopatch or laser adjuvantation) require significant energy to enter the skin (30-90 mJ). Within this study, we explore a way to more effectively use energy for skin penetration and vaccination. These modifications change the Nanopatch projections from cylindrical/conical shapes with a density of 20,000 per cm(2) to flat-shaped protrusions at 8,000 per cm(2), whilst maintaining the surface area and volume that is placed within the skin. We show that this design results in more efficient surface crack initiations, allowing the energy to be more efficiently be deployed through the projections into the skin, with a significant overall increase in penetration depth (50%). Furthermore, we measured a significant increase in localized skin cell death (>2 fold), and resultant infiltrate of cells (monocytes and neutrophils). Using a commercial seasonal trivalent human influenza vaccine (Fluvax 2014), our new patch design resulted in an immune response equivalent to intramuscular injection with approximately 1000 fold less dose, while also being a practical device conceptually suited to widespread vaccination.
微器件在过去十年中得到了广泛应用,其具有使用方便、无痛、稳定的固体配方和更好的免疫反应生成等优点。然而,高度免疫原性设备(例如基因枪、纳米贴或激光佐剂)的设计需要大量的能量才能进入皮肤(30-90mJ)。在本研究中,我们探索了一种更有效地利用能量进行皮肤穿透和接种疫苗的方法。这些修改将纳米贴的突起从圆柱形/圆锥形形状(每平方厘米 20000 个)改为每平方厘米 8000 个的扁平形状突起,同时保持放置在皮肤内的表面积和体积。我们发现,这种设计导致更有效的表面裂纹起始,使能量更有效地通过突起部署到皮肤中,穿透深度显著增加(50%)。此外,我们测量到局部皮肤细胞死亡(增加 2 倍以上)和浸润细胞(单核细胞和中性粒细胞)显著增加。使用商业化的季节性三价人类流感疫苗(Fluvax 2014),我们的新型贴片设计产生了相当于肌肉注射的免疫反应,剂量减少了约 1000 倍,同时也是一种实用的设备概念,适合广泛接种疫苗。