Hasan Mahadi, Khatun Anowara, Kogure Kentaro
Division of Animal Disease Model, Research Center for Experimental Modeling of Human Disease, Kanazawa University, Kanazawa 920-8640, Japan.
Graduate School of Biomedical Sciences, Tokushima University, Shomachi 1, Tokushima 770-8505, Japan.
Pharmaceutics. 2022 Feb 26;14(3):525. doi: 10.3390/pharmaceutics14030525.
Over the last few decades, biological macromolecular drugs (e.g., peptides, proteins, and nucleic acids) have become a significant therapeutic modality for the treatment of various diseases. These drugs are considered superior to small-molecule drugs because of their high specificity and favorable safety profiles. However, such drugs are limited by their low oral bioavailability and short half-lives. Biological macromolecular drugs are typically administrated via invasive methods, e.g., intravenous or subcutaneous injections, which can be painful and induce needle phobia. Noninvasive transdermal delivery is an alternative administration route for the local and systemic delivery of biological macromolecular drugs. However, a challenge with the noninvasive transdermal delivery of biological macromolecular drugs is the outermost layer of the skin, known as the stratum corneum, which is a physical barrier that restricts the entry of extraneous macromolecules. Iontophoresis (IP) relies on the application of a low level of electricity for transdermal drug delivery, in order to facilitate the skin permeation of hydrophilic and charged molecules. The IP of several biological macromolecular drugs has recently been investigated. Herein, we review the IP-mediated noninvasive transdermal delivery of biological macromolecular drugs, their routes of skin permeation, their underlying mechanisms, and their advance applications.
在过去几十年中，生物大分子药物（如肽、蛋白质和核酸）已成为治疗各种疾病的重要治疗方式。由于这些药物具有高特异性和良好的安全性，它们被认为优于小分子药物。然而，此类药物受到口服生物利用度低和半衰期短的限制。生物大分子药物通常通过侵入性方法给药，如静脉注射或皮下注射，这可能会引起疼痛并导致针头恐惧症。非侵入性经皮给药是生物大分子药物局部和全身给药的另一种途径。然而，生物大分子药物非侵入性经皮给药面临的一个挑战是皮肤的最外层，即角质层，它是一种物理屏障，限制了外来大分子的进入。离子电渗疗法（IP）依靠施加低水平的电流进行经皮给药，以促进亲水性和带电分子的皮肤渗透。最近已经研究了几种生物大分子药物的离子电渗疗法。在此，我们综述了离子电渗疗法介导的生物大分子药物非侵入性经皮给药、它们的皮肤渗透途径、潜在机制及其前沿应用。
