Using gold nanoparticles for enhanced intradermal delivery of poorly soluble auto-antigenic peptides

Singh, Ravinder K., Malosse, Camille, Davies, Joanne, Malissen, Bernard, Kochba, Efrat, Levin, Yotam, Birchall, James C. ORCID: https://orcid.org/0000-0001-8521-6924, Coulman, Sion A ORCID: https://orcid.org/0000-0002-1277-7584, Mous, Jan, McAteer, Martina A., Dayan, Colin M. ORCID: https://orcid.org/0000-0002-6557-3462, Henri, Sandrine and Wong, F. Susan ORCID: https://orcid.org/0000-0002-2812-8845 2021. Using gold nanoparticles for enhanced intradermal delivery of poorly soluble auto-antigenic peptides. Nanomedicine: Nanotechnology, Biology and Medicine 32 , 102321. 10.1016/j.nano.2020.102321

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Abstract

Ultra-small 1-2 nm gold nanoparticles (NP) were conjugated with a poorly-soluble peptide auto-antigen, associated with type 1 diabetes, to modify the peptide pharmacokinetics, following its intradermal delivery. Peptide distribution was characterized, in vivo, after delivery using either conventional intradermal injection or a hollow microneedle device. The poorly-soluble peptide was effectively presented in distant lymph nodes (LN), spleen and draining LN when conjugated to the nanoparticles, whereas peptide alone was only presented in the draining LN. By contrast, nanoparticle conjugation to a highly-soluble peptide did not enhance in vivo distribution. Transfer of both free peptide and peptide-NPs from the skin to LN was reduced in mice lacking lymphoid homing receptor CCR7, suggesting that both are actively transported by migrating dendritic cells to LN. Collectively, these data demonstrate that intradermally administered ultra-small gold nanoparticles can widen the distribution of poorly-soluble auto-antigenic peptides to multiple lymphoid organs, thus enhancing their use as potential therapeutics.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy Medicine
Publisher:	Elsevier
ISSN:	1549-9634
Date of First Compliant Deposit:	7 December 2020
Date of Acceptance:	23 October 2020
Last Modified:	11 Nov 2024 20:00
URI:	https://orca.cardiff.ac.uk/id/eprint/136850

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