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

Abstract

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Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes

“…The Investigational medicinal product (IMP) was C19-A3 GNP (Midacore™), which comprises GNPs [ 30 , 35 ] of a size of less than 5 nm, covalently coupled to an 18-amino acid human peptide, the sequence of which is identical to the residues from position 19 in the C-peptide of proinsulin through to position 3 on the A-chain of the same molecule (GSLQPLALEGSLQKRGIV). The peptide is synthesised with a linker to facilitate binding to the GNPs: 3-mercaptopropionyl-SLQPLALEGSLQKRGIV 2 acetate salt (disulfide bond).…”

Application of microneedle patches for drug delivery; doorstep to novel therapies

“…Data indicated an increased T lymphocyte proliferation in distant lymphoid organs like pancreatic lymphoid nodes. 130 The combination of peptides and nanoparticles promoted T cell expansion in remote areas like lymphoid nodes, draining lymphoid, spleen, and pancreatic lymphoid nodes after 48 h while T cell proliferation via peptide in the absence of gold nanoparticles was only seen in draining lymphoid nodes after 72 h. 130 Moreover, these values were insignificantly modified through the MN delivery system when compared to subcutaneous injection. Additionally, the existence of a higher affinity of water-soluble peptides to T lymphocytes leads to cellular proliferation and significant distribution related to less-soluble peptides.…”

“…Notably, the combination of water-soluble peptides and nanoparticles reduced the functionality of water-soluble peptides. 130 This strategy decreased the expression of IFN-γ in the auxiliary lymphoid nodes after 3 days. 130 In CCR7 -/- mice, the immune response is blunted due to the lack of CCR7 and diminished dendritic cell homing in lymphoid nodes.…”

“… 130 This strategy decreased the expression of IFN-γ in the auxiliary lymphoid nodes after 3 days. 130 In CCR7 -/- mice, the immune response is blunted due to the lack of CCR7 and diminished dendritic cell homing in lymphoid nodes. The combination of gold nanoparticles plus peptide and peptide alone were distributed to lymphoid nodes through dermal dendritic cell migration and proliferation.…”

“…The combination of gold nanoparticles plus peptide and peptide alone were distributed to lymphoid nodes through dermal dendritic cell migration and proliferation. 130 …”