Transdermal Administration of Nanobody Molecules using Hydrogel-Forming Microarray Patch Technology: A Unique Delivery Approach

Abstract

Nanobody molecules, derived from heavy-chain only antibodies in camelids, represent the next generation of biotherapeutics. In addition to low immunogenicity, high stability, and potency, their single-domain format facilitates the construction of multivalent molecules for therapeutic applications. Although predominantly administered using a hypodermic syringe and needle, alternative delivery methods are under investigation. That said, the transdermal route has yet to be explored. Therefore, microarray patch (MAP) technology, offering a potentially high dose, pain-free transdermal system, is employed in this study. Trivalent Nanobody molecules, with and without half-life extension (VHH and VHH[HLE]), are formulated into hydrogel-forming MAPs, with pharmacokinetic parameters assessed in Sprague–Dawley rats. VHH MAPs exhibited a sustained release profile, with a serum concentration of 19 ± 9 ng mL⁻¹ 24 h post-administration. In contrast, a subcutaneous (SC) injection showed faster clearance, with a serum concentration of 1.1 ± 0.4 ng mL⁻¹ at 24 h. For VHH(HLE), both SC and MAP cohorts achieved a maximum serum concentration (T_max) at 24 h. The MAP cohort displayed a notable increase in VHH(HLE) serum levels between 6–24 h, dropping after MAP removal. This study has exemplified MAPs potential for delivering advanced biologics, indicating the transdermal route's promise for pain-free, patient-friendly administration of Nanobody molecules.