Intradermal Delivery of Naked mRNA Vaccines via Iontophoresis

Abstract

Messenger RNA (mRNA) vaccines against infectious diseases and for anticancer immunotherapy have garnered considerable attention. Currently, mRNA vaccines encapsulated in lipid nanoparticles are administrated via intramuscular injection using a needle. However, such administration is associated with pain, needle phobia, and lack of patient compliance. Furthermore, side effects such as fever and anaphylaxis associated with the lipid nanoparticle components are also serious problems. Therefore, noninvasive, painless administration of mRNA vaccines that do not contain other problematic components is highly desirable. Antigen-presenting cells reside in the epidermis and dermis, making the skin an attractive vaccination site. Iontophoresis (ItP) uses weak electric current applied to the skin surface and offers a noninvasive permeation technology that enables intradermal delivery of hydrophilic and ionic substances. ItP-mediated intradermal delivery of biological macromolecules has also been studied. Herein, we review the literature on the use of ItP technology for intradermal delivery of naked mRNA vaccines which is expected to overcome the challenges associated with mRNA vaccination. In addition to the physical mechanism, we discuss novel biological mechanisms of iontophoresis, particularly ItP-mediated opening of the skin barriers and the intracellular uptake pathway, and how the combined mechanisms can allow for effective intradermal delivery of mRNA vaccines.

Prospects and Challenges in Developing mRNA Vaccines for Infectious Diseases and Oncogenic Viruses

“…To date, 17 mRNA vaccines are under clinical research for COVID-19 prevention. The speed and ease of mRNA vaccine production make it a promising technology for responding to fresh changes in the viral genome, such as those that have emerged during the COVID-19 pandemic [52][53][54][55][56].…”

“…Chen and Kim (2022) discussed approaches to enhancing the thermostability of mRNA vaccines by incorporating stabilizing agents and modifying RNA structures. These strategies aimed to protect the mRNA molecule from degradation under different temperature conditions, ensuring vaccine efficacy and extending shelf life [56]. Formulation strategies are being developed to address stability challenges in mRNA vaccines.…”