Biocompatible ionic liquids assisted transdermal co-delivery of antigenic protein and adjuvant for cancer immunotherapy
Biocompatible ionic liquids assisted transdermal co-delivery of antigenic protein and adjuvant for cancer immunotherapy
复制标题
DOI：
10.1016/j.ijpharm.2021.120582
复制
发表时间：
2021-04-23
影响因子：
5.8
通讯作者：
Goto, Masahiro
中科院分区：
文献类型：
--
作者：
Chowdhury, Md Raihan;Moshikur, Rahman Md;Goto, Masahiro
人体皮肤含有大量抗原呈递细胞，这些细胞是多种免疫疗法的潜在靶点，包括疫苗接种和癌症免疫疗法。然而，皮肤的最外层——角质层——作为一个主要的物理屏障，阻止分子量为50 - 500 Da的抗原的渗透。在这项研究中，开发了一种离子液体辅助递送系统（ILDS），该系统能够成功地经皮递送抗原蛋白卵清蛋白（OVA），并以toll样受体激动剂咪喹莫特作为佐剂，刺激特异性免疫反应。离子液体和ILDS均具有完全的生物相容性，可用于局部或透皮治疗。由于在ILDS中掺入了表面活性离子液体，抗原蛋白和佐剂的皮肤渗透性被发现显著增强。一项体内免疫研究表明，由于抗原和佐剂在皮肤中的渗透增强，ov特异性IgG抗体的产生水平很高。在一项预防性抗癌研究中，与对照组相比，通过ILDS接种疫苗显示出更强的肿瘤生长抑制作用。这些结果表明，ILDS可能是一种有前途的透皮免疫治疗策略。
Human skin contains numerous antigen-presenting cells that are a potential target for several immune-based therapies, including vaccination and cancer immunotherapy. However, the outermost layer of the skin-the stratum corneum-acts as a major physical barrier against the permeation of antigens that have a molecular weight > 500 Da. In this study, an ionic liquid-assisted delivery system (ILDS) was developed, which enabled the successful transdermal delivery of an antigenic protein, ovalbumin (OVA), with a toll-like receptor agonist, imiquimod, as an adjuvant, to stimulate a specific immune response. Both the ionic liquids and ILDS were completely biocompatible for topical or transdermal application for therapeutic purposes. The skin permeation of the antigenic protein and adjuvant was found to be significantly enhanced because of the incorporation of a surface-active ionic liquid in the ILDS. An in vivo immunization study showed that there was a high level of OVAspecific IgG antibody production because of the enhanced permeation of the antigen and adjuvant across and into the skin. In a preclusive anticancer study, vaccination through ILDS showed stronger tumor-growth inhibition compared to control group. These results indicated that the ILDS could be a promising strategy for transdermal immunization as future therapeutics.