Transdermal delivery of heavy chain only antibody binding domains using hydrogel-forming microarray patches

Abstract

Since the licensing of the first monoclonal antibody (mAb) over 30 years ago, the mAb industry has expanded exponentially, with six of the top 10 blockbuster drugs in 2018 being antibody-based. However, rather than resting on their laurels, drug developers have continued to innovate. This has led to the development of ‘next generation’ biologics which have been designed to overcome the size and stability limitations associated with mAbs. This new era of biotechnology incorporates heavy chain only antibodies (HCAbs) such as Nanobody® molecules and VNARs, derived from camelids and sharks, respectively. Owing to their small size (~13 kDa) and reduced complexity, they are less expensive to produce than mAbs. Furthermore, their potency has been shown to be an order of magnitude higher than the best-selling mAb-based drug currently on the market, Humira®. This has enabled other methods of administration to be investigated, such as the oral, pulmonary and ocular routes. However, transdermal delivery of HCAbs has yet to be examined. Therefore, this thesis explores the transdermal delivery of both VNARs and Nanobody® molecules using hydrogel-forming microarray patches (MAPs). Using this MAP technology, both HCAbs could permeate through dermatomed (350 µm) neonatal porcine skin in vitro. Furthermore, two Nanobody® molecules were successfully delivered in a Sprague Dawley rat model for the first time. Therefore, the MAP system developed in this thesis has supported the transdermal delivery of ‘next generation’ biotherapeutics. This thesis also aimed to address the requests of patients from a previous study by designing a novel feedback mechanism to confirm complete MAP skin insertion. With further modification, this could help facilitate successful MAP commercialisation.

Thesis embargoed until 31 July 2027.

Date of Award	Jul 2022
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Northern Ireland Department for the Economy
Supervisor	Ryan Donnelly (Supervisor) & Christopher Scott (Supervisor)