Enhancing the Transdermal Delivery of ‘Next Generation’ Variable New Antigen Receptors Using Microarray Patch Technology: a Proof-of-Concept Study

A.R.J. Hutton, O. Ubah, C. Barelle, R.F. Donnelly

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Heavy chain only binding proteins, such as variable new antigen receptors (VNARs), have emerged as an alternative to the highly successful therapeutic monoclonal antibodies (mAb). Owing to their small size (» 11 kDa)
and single chain only architecture, they are amenable to modular reformatting and can be produced using inexpensive expression systems. Furthermore, due to their low molecular weight (MW) and high stability, they
may be suitable for alternative delivery strategies, such as microarray array patches (MAPs). In this study, the
transdermal delivery of ELN22-104, a multivalent anti-hTNF-a VNAR, was examined using both dissolving and
hydrogel-forming MAPs. For dissolving MAPs, the cumulative in vitro permeation of ELN22-104 reached a plateau after 2 h (12.24 § 0.17 mg). This could be important for bolus dosing. Assessing two hydrogel-forming
MAPs in vitro, PVP/PVA hydrogel-forming MAPs delivered significantly higher drug doses when compared to
‘super swelling’ MAPs, equivalent to 43.13 § 10.36 mg and 23.13 § 5.66 mg, respectively (p < 0.05). Consequently, this study has proven that by modifying the MAP system, the transdermal delivery of a VNAR across
the skin can be enhanced. Furthermore, this proof-of-concept study has shown that transdermal delivery of
‘next generation’ biotherapeutics is achievable using MAP technology.
Original languageEnglish
Pages (from-to)3362-3376
Number of pages15
JournalJournal of Pharmaceutical Sciences
Volume111
Issue number12
Early online date26 Aug 2022
DOIs
Publication statusPublished online - 26 Aug 2022

Keywords

  • Microarray patches (MAPs)
  • Transdermal
  • Monoclonal antibodies (mAb)
  • Molecular weight (MW)

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