Dissolving microneedles (DMNs) are used for minimally invasive transdermal drug delivery. Dissolution of drugs is achieved in the body after skin penetration by DMNs. Unlike injections, the insertion depth of the DMN is an important issue because the amount of dissolved DMN in the skin determines the amount of drug delivered. Therefore, the inaccurate drug delivery due to the incomplete insertion is one of the limitations of the DMN. Thus, many insertion and penetration tests have been essentially conducted in DMN studies, yet only incomplete insertion is known and the exact standard for how much it is not inserted is still unknown. Moreover, there are various shapes have been introduced in the microneedle field, there have been only few studies that have compared and evaluated the insertion depth of the shapes. Here, we present an intensive approach for DMN insertion based on DMN shape among various insertion deciding factors. We numerically analyzed the volumetric distribution of three types of DMN shapes: conical-shaped DMN, funnel-shaped DMN, and candlelit-shaped DMN, and introduced a new insertion evaluation criterion while covering previous insertion evaluations. Using optical coherence tomography, the images of DMNs embedded in the skin were analyzed in rea l-time, and the amount of drug delivered was analyzed at sectioned depth with a cryotome. The in vitro data confirmed that the insertion depth differed based on shape, and the resulting drug delivery depended on the volume assigned to the insertion depth. Insulin-loaded DMNs were applied to C57BL/6 mice, and the results of pharmacokinetic and pharmacodynamic analyses supported the results of the in vitro analysis. Our approach, which considers the correlation between DMN shape and insertion depth, will contribute to establishing criteria for various DMN design and maximizing drug delivery.
|Publication status||Published - 2023 Feb|
Bibliographical noteFunding Information:
This research was supported by the Korea Medical Device Development Fund grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, Republic of Korea, the Ministry of Food and Drug Safety) (Project Number: 1711138200 , RS-2020-KD000111 ), by the Development of original technologies for the nextgen vaccines for infectious diseases of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. 2022M3E5F1044123 ), by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number : HV22C0084 ), and by the B rain Korea 21 (BK21) FOUR program . H. Min, Y. Kim, J. Nam, H. Ahn, and M. Kim are fellowship awardee by BK21 FOUR program. In addition, this work was supported by the Hyundai Motor Chung Mong-Koo Foundation .
© 2022 Elsevier B.V.
All Science Journal Classification (ASJC) codes
- Biomedical Engineering