Transdermal delivery of interferon-gamma (IFN-gamma) mediated by penetratin, a cell-permeable peptide.
IFN-gamma (interferon-gamma) has several applications in the treatment of IFN-gamma-related skin disorders. While systemic delivery - the major route used to administer IFN-gamma - results in significant side effects and toxicity, including fever, fatigue, nausea, vomiting and neurotoxicity, transdermal delivery has a very low transduction efficiency. In order to improve the efficiency of transdermal IFN-gamma delivery, we introduced a Pen (penetratin) peptide, a 16-amino-acid-long polypeptide corresponding to the third helix of the DNA-binding domain (homoeodomain) of Antennapedia (a Drosophila transcription factor). The human IFN-gamma gene was then fused with a gene fragment that encodes the Pen of Antennapedia in a bacterial expression vector, producing a genetic in-frame Pen-IFN-gamma. The expressed and purified Pen-IFN-gamma was then found to have a much more efficient transduction profile than native IFN-gamma. In addition, compared with native IFN-gamma, Pen-IFN-gamma exhibited similar activities when added exogenously to a culture medium: (i) induction of IRF-1 gene expression, and (ii) NF-kappaB (nuclear factor kappaB) luciferase reporter activation. These results indicate that the transdermal delivery system using Pen may be an excellent way to replenish IFN-gamma in the various disorders related to this cytokine.
Lee
Jongsung
J
Department of Skin Cell Biology, Biospectrum Life Science Institute, 101-701 SK Ventium, 522 Dangjung Dong, Gunpo City, Gyunggi Do 435-776, Republic of Korea.
Jung
Eunsun
E
Park
Junho
J
Park
Deokhoon
D
D000279:Administration, Cutaneous; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000502:physiology*; D057846:Cell-Penetrating Peptides; D003876:Dermatitis, Atopic / Q000188:drug therapy; D020405:Dermis / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics / Q000627:therapeutic use; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000493:pharmacokinetics / Q000627:therapeutic use
D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma; C414409:penetratin