Ionic Liquid-Enabled Topical Delivery of Immunomodulators,ACS Biomaterials Science & Engineering

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Ionic Liquid-Enabled Topical Delivery of Immunomodulators
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2021-05-13 , DOI: 10.1021/acsbiomaterials.1c00322
Zongmin Zhao _{1,

2} , Eden E L Tanner ₁ , Jayoung Kim ₁ , Kelly Ibsen ₁ , Yongsheng Gao ₁ , Samir Mitragotri _{1,

2}

Affiliation

Skin is one of the most immunologically active organs of the body due to the presence of diverse immune cells and its active involvement in the innate and adaptive immunity. Because of its unique location and immunological role, skin offers an excellent site for the introduction of immunomodulators to synergize with the active immune microenviroment for the desired outcome. However, delivery of immunomodulators to the skin remains a significant challenge due to the skin’s barrier properties. Here, we report an ionic liquid (IL)-based strategy to formulate and deliver immunomodulators to the skin. Using imiquimod (IMQ) and triamcinolone acetonide (TCA) as the respective model immunoactive and immunosuppressive drugs, we demonstrated that ILs significantly enhanced the solubility of immunomodulators. In addition, ILs enabled the formulation of the immunomodulators into stable, topically applicable forms. Our ex vivo skin penetration studies revealed that the IL formulations outperformed respective commercial topical comparators and delivered significantly more immunomodulators to deep skin layers. The lead IMQ formulation exhibited >10-fold better efficacy in delivering IMQ to the deep skin layers as compared to the commercial 5% IMQ cream. Lead TCA formulations achieved a dose level in deep skin layers that is comparable to that by clinically used intralesional injections. Our data collectively suggest that the IL-based strategy can be a simple and effective platform for delivery of immunomodulators to the skin.

中文翻译：

免疫调节剂的离子液体局部递送

由于存在多种免疫细胞并积极参与先天免疫和适应性免疫，皮肤是人体免疫学最活跃的器官之一。由于其独特的位置和免疫作用，皮肤为引入免疫调节剂提供了一个极好的场所，以与活跃的免疫微环境协同作用，达到预期的效果。然而，由于皮肤的屏障特性，向皮肤递送免疫调节剂仍然是一个重大挑战。在这里，我们报告了一种基于离子液体 (IL) 的策略，用于配制和递送免疫调节剂至皮肤。使用咪喹莫特 (IMQ) 和曲安奈德 (TCA) 作为各自的模型免疫活性和免疫抑制药物，我们证明了 ILs 显着增强了免疫调节剂的溶解度。此外，ILs 能够将免疫调节剂制成稳定的、局部适用的形式。我们的离体皮肤渗透研究表明，IL 制剂的性能优于各自的商业局部比较剂，并向深层皮肤层递送显着更多的免疫调节剂。与市售的 5% IMQ 乳膏相比，领先的 IMQ 配方在将 IMQ 输送到深层皮肤方面表现出更好的 10 倍以上。铅 TCA 制剂在深层皮肤层中达到的剂量水平与临床使用的病灶内注射相当。我们的数据共同表明，基于 IL 的策略可以成为将免疫调节剂递送至皮肤的简单而有效的平台。

更新日期：2021-06-14

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