Drug Delivery · Available online 12 May 2026 · In press · DOI 10.1080/10717544.2026.2667564
Changzhao Jiang, Jing Yang, Mengxuan Gao, Yi He, Weiwei Liao, Hang Chen, Zhixiong Wang, Shibo Ying, Xiaohua Tao, Xiumei Jiang, Jincui Ye
Separable bubble microneedles (BMNs) incorporate an internal cavity that enables tip-confined loading and controlled tip-baseplate separation, yet their design has largely relied on empirical iteration. Here, we present a finite element analysis (FEA)-guided co-design framework that co-optimizes BMN geometry, cavity parameters, and matrix properties to enable controlled tip-baseplate separation while preserving insertion robustness. Simulations predicted stress localization at the engineered cavity, thereby reducing the transverse separation force without compromising axial failure load. Using minoxidil sulfate-loaded BMNs (MXS-BMNs) and insulin-loaded BMNs (INS-BMNs) as transdermal and sublingual models, respectively, the measured transverse separation forces were 5.23 N and 4.17 N, compared with FEA predictions of 6.16 N and 4.79 N. The corresponding axial failure loads were 0.13 N and 0.28 N, exceeding reported penetration thresholds for skin and sublingual mucosa. Release studies showed that more than 80% of the payload was liberated within 10 min. In ex vivo Franz diffusion tests, MXS-BMNs achieved approximately sevenfold greater cumulative minoxidil permeation over 24 h than an equivalent-dose topical gel. In vivo, MXS-BMNs accelerated hair regrowth in C57BL/6 mice, and INS-BMNs produced rapid and sustained glucose lowering in diabetic rats comparable to subcutaneous injection via an injection-free mucosal route. Collectively, this work establishes a semi-quantitative screening approach that reduces empirical iteration and expedites the development of separable microneedle systems for rapid transdermal and sublingual delivery.
Abstract from DOAJ. Public domain (CC0 1.0).
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Jiang, C., Yang, J., Gao, M., et al. (2026). FEA-guided co-design of bubble microneedles: controlled tip separation for rapid transdermal and sublingual delivery. Drug Delivery. https://doi.org/10.1080/10717544.2026.2667564