Penetratin is a cell-penetrating peptide (CPP), also known as a protein transduction domain (PTD), of which the first 16 amino acids are derived from the third helix of the Antennapedia protein homeodomain. Penetratin linked to a phosphodiester oligonucleotide is capable of permeating through neuronal cell membranes and down-regulating genes.
Nasal vaccination is considered an attractive strategy to prevent the infection and spread of viruses. However, the vaccine formulations available on the market remain imperfect on account of their limited effectiveness. In the present study, we hypothesized that the nasal coadministration of antigens with cell-penetrating peptides promotes antigen delivery immune response in the nasal mucosa, thereby enhancing the production of mucosal IgA and systemic IgG. The levels of ovalbumin (OVA)-specific IgG and IgA in plasma and nasal perfusate, respectively, increased after 2 or 4 weeks on nasal coadministration of OVA with l- or d-penetratin, suggesting that OVA antigen was effectively delivered by penetratin to the nasal epithelium. An additional study demonstrated that the production of systemic IgG and nasal mucosal IgA against influenza A virus was specifically promoted by nasal coadministration of influenza A virus with d-penetratin. The results of this study suggested that cell-penetrating peptides are a promising tool for the delivery of vaccines to the nasal mucosa and for the subsequent dual stimulation of systemic and mucosal immune responses.
2- Nielsen EJ, Kamei N, Takeda-Morishita M. Biol Pharm Bull. (2015)
Novel delivery technology using cell-penetrating peptides (CPPs) such as Penetratin have recently shown their potential and are emerging as promising candidates for an oral protein and peptide delivery systems. As with for the development of any absorption enhancer that is meant to function across an epithelial layer covering a surface highly exposed to pathogens such as the intestines, concern arises about the safety of such enhancers. The purpose of this study was to investigate the effect of 7 d of consecutive oral administrations of CPPs and a typical enterotoxin, lipopolysaccharide (LPS) to mice to determine the degree, if any, of damage caused to the hepatic tissue. Following the 7-d dosing regimen, we could not detect significantly increased levels of the liver enzymes alanine aminotransferase and aspartate aminotransferase in plasma of mice treated with CPP (such as Penetratin) and LPS compared to the controls, whereas heightened levels were observed in animals receiving the bile salt. In conclusion, the repeated use of CPPs (especially Penetratin) as an oral absorption enhancer for macromolecules was found to be a safe strategy
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