Transdermal Administration of Nanobody Molecules Using Hydrogel‐Forming Microarray Patch Technology: A Unique Delivery Approach

AbstractNanobody 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 (Tmax) 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.