Wu Jiayu, Zuo Jun, Dou Wei, Wang Ke, Long Jinrong, Yu Changxiao, Miao Yiqi, Liao Yuqin, Li Yanyan, Cao Yiming, Lu Lu, Jin Yiguang, Zhang Bo, Yang Jing
Department of Pharmacy & State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, People's Republic of China; Bioinformatics Center of AMMS, Beijing, People's Republic of China.
Bioinformatics Center of AMMS, Beijing, People's Republic of China.
Int J Pharm. 2025 Apr 15;674:125427. doi: 10.1016/j.ijpharm.2025.125427. Epub 2025 Mar 10.
Traditional mRNA vaccine formulation loaded by lipid nanoparticle (mRNA-LNP) has several shortcomings in clinical application, including the need for cryopreservation, discomfort associated with intramuscular injections, and the risk of liver aggregation. Dissolvable microneedles (DMNs), as a novel transdermal drug delivery platform, can overcome the skin barrier to deliver drugs directly into the skin in a minimally invasive manner. However, mRNA-LNP is unstable and easily degraded during the solidification of DMN. In this study, we proposed to establish a rapidly dissolvable bubble microneedle patch (bMNP) system for the transdermal delivery of mRNA-LNP. We explored to use polyvinyl alcohol (PVA) and trehalose for the first time as matrix material for preparing microneedles. Our results demonstrate that the stability of the mRNA-LNP was obviously improved. The mRNA in this bMNP system can be stored at room temperature for at least one month. Furthermore, the existence of air bubbles between the needle tip and the dorsal scale of bMNP can achieve dorsal scale separation by applying shear force after inserting into subcutaneous tissue, and effectively target lymph nodes in vivo after releasing mRNA-LNP. Using mRNA that encodes the spike protein from SARS-CoV-2 as a test case, the rapidly separable bMNP system induced the production of significant levels of spike-specific IgG antibodies, neutralizing antibodies, and a Th1-polarized T cell response, providing an alternative route for mRNA delivery. Our research is expected to provide a promising transdermal drug delivery strategy that can improve mRNA vaccine accessibility.
由脂质纳米颗粒负载的传统信使核糖核酸疫苗制剂（mRNA-LNP）在临床应用中有几个缺点，包括需要冷冻保存、与肌肉注射相关的不适以及肝脏聚集的风险。可溶解微针（DMN）作为一种新型的经皮给药平台，可以克服皮肤屏障，以微创方式将药物直接递送至皮肤。然而，mRNA-LNP在DMN固化过程中不稳定且容易降解。在本研究中，我们提出建立一种用于mRNA-LNP经皮递送的快速溶解气泡微针贴片（bMNP）系统。我们首次探索使用聚乙烯醇（PVA）和海藻糖作为制备微针的基质材料。我们的结果表明，mRNA-LNP的稳定性明显提高。该bMNP系统中的mRNA可以在室温下储存至少一个月。此外，bMNP针尖与背鳞之间存在气泡，插入皮下组织后施加剪切力可实现背鳞分离，并在释放mRNA-LNP后在体内有效靶向淋巴结。以编码严重急性呼吸综合征冠状病毒2刺突蛋白的mRNA作为测试案例，这种快速可分离的bMNP系统诱导产生了显著水平的刺突特异性IgG抗体、中和抗体以及Th1极化的T细胞反应，为mRNA递送提供了一条替代途径。我们的研究有望提供一种有前景的经皮给药策略，可提高mRNA疫苗的可及性。
