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Transcutaneous Cancer Vaccine Using a Reverse Micellar Antigen Carrier.
Molecular Pharmaceutics ( IF 4.9 ) Pub Date : 2019-12-31 , DOI: 10.1021/acs.molpharmaceut.9b01104
Shuto Kozaka , Yoshiro Tahara , Rie Wakabayashi , Takahiro Nakata 1 , Taro Ueda 1 , Noriho Kamiya , Masahiro Goto
Affiliation  

Skin dendritic cells (DCs) such as Langerhans cells and dermal dendritic cells have a pivotal role in inducing antigen-specific immunity; therefore, transcutaneous cancer vaccines are a promising strategy to prophylactically prevent the onset of a variety of diseases, including cancers. The largest obstacle to delivering antigen to these skin DC subsets is the barrier function of the stratum corneum. Although reverse micellar carriers are commonly used to enhance skin permeability to hydrophilic drugs, the transcutaneous delivery of antigen, proteins, or peptides has not been achieved to date because of the large molecular weight of drugs. To achieve effective antigen delivery to skin DCs, we developed a novel strategy using a surfactant as a skin permeation enhancer in a reverse micellar carrier. In this study, glyceryl monooleate (MO) was chosen as a skin permeation enhancer, and the MO-based reverse micellar carrier enabled the successful delivery of antigen to Langerhans cells and dermal dendritic cells. Moreover, transcutaneous vaccination with the MO-based reverse micellar carrier significantly inhibited tumor growth, indicating that it is a promising vaccine platform against tumors.

中文翻译:

使用反向胶束抗原载体的经皮癌疫苗。

皮肤树突状细胞(DC),如朗格汉斯细胞和真皮树突状细胞在诱导抗原特异性免疫中起关键作用。因此,经皮癌疫苗是一种预防性地预防包括癌症在内的多种疾病发作的有前途的策略。将抗原递送至这些皮肤DC亚群的最大障碍是角质层的屏障功能。尽管通常使用反胶束载体来增强皮肤对亲水性药物的渗透性,但是由于药物的分子量大,迄今为止尚未实现抗原,蛋白质或肽的透皮递送。为了实现向皮肤DC的有效抗原递送,我们开发了一种新的策略,使用表面活性剂作为逆胶束载体中的皮肤渗透促进剂。在这项研究中,选择单油酸甘油酯(MO)作为皮肤渗透促进剂,基于MO的逆胶束载体使抗原能够成功地传递给Langerhans细胞和真皮树突状细胞。而且,基于MO的逆胶束载体的经皮疫苗接种显着抑制了肿瘤的生长,这表明它是针对肿瘤的有希望的疫苗平台。
更新日期:2019-12-31
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