TY - JOUR
T1 - Transdermal administration of nanobody molecules using hydrogel-forming microarray patch technology: a unique delivery approach
AU - Hutton, Aaron R. J.
AU - Kirkby, Melissa
AU - Van Bogaert, Tom
AU - Casteels, Peter
AU - Nonne, Christelle
AU - De Brabandere, Veronique
AU - Van de Vyver, Ortwin
AU - Vora, Lalit K.
AU - Tekko, Ismaiel A.
AU - McCarthy, Helen O.
AU - Donnelly, Ryan F.
PY - 2024/6
Y1 - 2024/6
N2 - 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.
AB - 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.
KW - General Chemical Engineering
KW - Materials Chemistry
KW - Organic Chemistry
KW - Polymers and Plastics
U2 - 10.1002/mame.202400029
DO - 10.1002/mame.202400029
M3 - Article
SN - 1439-2054
VL - 309
JO - Macromolecular Materials and Engineering
JF - Macromolecular Materials and Engineering
IS - 6
M1 - 2400029
ER -