Department of Bioengineering, University of California (UC), Berkeley, Berkeley, CA 94720, USA.
School of Applied Life Sciences, Keck Graduate Institute, Claremont, CA 91711, USA.
Sci Transl Med. 2017 Mar 8;9(380). doi: 10.1126/scitranslmed.aaf6413.
Noninvasive immunization technologies have the potential to revolutionize global health by providing easy-to-administer vaccines at low cost, enabling mass immunizations during pandemics. Existing technologies such as transdermal microneedles are costly, deliver drugs slowly, and cannot generate mucosal immunity, which is important for optimal immunity against pathogens. We present a needle-free microjet immunization device termed MucoJet, which is a three-dimensional microelectromechanical systems-based drug delivery technology. MucoJet is administered orally, placed adjacent to the buccal tissue within the oral cavity, and uses a self-contained gas-generating chemical reaction within its two-compartment plastic housing to produce a high-pressure liquid jet of vaccine. We show that the vaccine jet ejected from the MucoJet device is capable of penetrating the buccal mucosal layer in silico, in porcine buccal tissue ex vivo, and in rabbits in vivo. Rabbits treated with ovalbumin by MucoJet delivery have antibody titers of anti-ovalbumin immunoglobulins G and A in blood serum and buccal tissue, respectively, that are three orders of magnitude higher than rabbits receiving free ovalbumin delivered topically by a dropper in the buccal region. MucoJet has the potential to accelerate the development of noninvasive oral vaccines, given its ability to elicit antibody production that is detectable locally in the buccal tissue and systemically via the circulation.
非侵入性免疫接种技术有可能通过低成本提供易于管理的疫苗来彻底改变全球健康，使其能够在大流行期间进行大规模免疫接种。现有的技术，如透皮微针，成本高，药物输送缓慢，并且不能产生粘膜免疫，而粘膜免疫对于针对病原体的最佳免疫至关重要。我们提出了一种称为 MucoJet 的无针微射流免疫接种装置，它是一种基于三维微机电系统的药物输送技术。MucoJet 通过口腔给药，放置在口腔内颊组织旁边，并在其两部分塑料外壳内使用自给式气体产生化学反应，产生疫苗的高压液体射流。我们表明，从 MucoJet 装置喷出的疫苗射流能够在计算机中穿透颊粘膜层，在猪颊组织中进行离体实验，并在兔子体内进行体内实验。通过 MucoJet 传递卵清蛋白的兔子在血清和颊组织中产生的抗卵清蛋白免疫球蛋白 G 和 A 的抗体滴度分别比通过在颊部用滴管局部给予游离卵清蛋白的兔子高三个数量级。鉴于 MucoJet 能够在局部在颊组织中并通过循环系统在全身范围内引发抗体产生，因此它有可能加速非侵入性口服疫苗的开发。
