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

• Published in: Nanomedicine Vol. 32; p. 102321
• Main Authors: Singh, Ravinder K., Malosse, Camille, Davies, Joanne, Malissen, Bernard, Kochba, Efrat, Levin, Yotam, Birchall, James C., Coulman, Sion A, Mous, Jan, McAteer, Martina A., Dayan, Colin M., Henri, Sandrine, Wong, F. Susan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2021; Elsevier
• Subjects: Amino Acid Sequence; Animals; Antigens - metabolism; Autoantigen; Cell Proliferation; Dendritic Cells - drug effects; Gold - chemistry; Gold nanoparticles; Hydrophobic; Immunology; Injections, Intradermal; Intradermal; Life Sciences; Metal Nanoparticles - chemistry; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microneedle; Needles; Peptide; Peptides - chemistry; Peptides - pharmacokinetics; Peptides - pharmacology; Phenotype; Skin - drug effects; Solubility; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Autoantigen; Peptide; Gold nanoparticles; Intradermal; Microneedle; Hydrophobic
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2020.102321

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. Soluble peptides, such as OTII, injected intradermally are carried to the draining LN and then can rapidly diffuse to all secondary lymphoid organs (a). Insoluble peptides, such as BDC2.5HIP are transported to the draining lymph node only (b). Complexing insoluble peptides, such as BDC2.5HIP, with small (1-2 nm) gold nanoparticles restores this wide distribution beyond the draining LN, allowing for intradermal administration to be used to modify immune responses in distant tissues, such as the pancreas in type 1 diabetes. [Display omitted]