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

• Published in: Macromolecular materials and engineering Vol. 309; no. 6
• Main Authors: Hutton, Aaron R. J., Kirkby, Melissa, Van Bogaert, Tom, Casteels, Peter, Nonne, Christelle, De Brabandere, Veronique, Vyver, Ortwin Van, Vora, Lalit K., Tekko, Ismaiel A., McCarthy, Helen O., Donnelly, Ryan F.
• Format: Journal Article
• Language: English
• Published: Weinheim John Wiley & Sons, Inc 01.06.2024; Wiley-VCH
• Subjects: biotherapeutics; Controlled release; Hydrogels; hydrogel‐forming; Immunogenicity; Life extension; microarray patch; Nanobodies; Pain; Pharmacokinetics; Serum levels; Sustained release; Syringes; Therapeutic applications; transdermal
• ISSN: 1438-7492; 1439-2054
• DOI: 10.1002/mame.202400029

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 (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. Nanobody molecules, derived from cameilds, possess high stability, affinity and potency. Currently, their transdermal delivery remains unexplored and are typically administered via needle and syringe. In this work, a hydrogel‐forming microarray patch (MAP) has been developed. Overall, this study has shown that MAPs have the potential to provide high dose delivery of Nanobody molecules across the skin for therapeutic applications.