Development of Soluble Microneedles for the Intradermal Delivery of Antigens and Vaccines

適用於皮內免疫抗原和疫苗遞送的可溶性微針的開發

Student thesis: Doctoral Thesis

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Award date12 Jan 2024

Abstract

The emergence of the COVID-19 pandemic has accelerated the clinical development of mRNA-based vaccines, such as Comirnaty and Spikevax. These vaccines have demonstrated powerful efficacy in human patients and have supported the development of various vaccines in recent years. Interestingly, current vaccines are administered to patients only through conventional injection methods. This presents certain limitations, such as pain, injection site inflammation, needle handling inconvenience, and the need for trained healthcare providers for administration. To overcome these limitations, this study investigates the delivery of various antigens using dissolvable microneedles. In addition, this article also explores the feasibility of using microneedles to deliver nanofluorescent probes. Micro-molding technology is employed for the cost-effective manufacturing of microneedles.

The first part of the study focuses on the development of protein delivery using microneedles. The delivery of SARS-CoV-2 proteins (spike receptor-binding domain protein and nucleocapsid protein) and adjuvants using hyaluronic acid-based microneedles (MNs) at room temperature induces strong humoral and cellular immune responses in mice after simple patch application and intradermal administration. Hyaluronic acid (HA) is a naturally occurring substance in the skin with high biodegradability. Importantly, MNs patches have the potential for future painless self-application, which could improve global vaccine compliance.

The second part of the study involves the development of mRNA delivery using cryogenic microneedle (CryoMNs). CryoMNs manufactured at ultra-low temperatures can be utilized for the delivery of temperature-sensitive mRNA vaccines, such as Comirnaty. Mice also exhibit significant humoral and cellular immune responses under the action of low-temperature MNs. This supports the possibility of using non-invasive MN devices for the administration of commercial vaccines in clinical settings.