title: Topical Delivery of Protein and Peptide Using Novel Cell Penetrating Peptide IMT-P8.
abstract: Skin, being the largest organ of the body, is an important site for drug administration. However, most of the drugs have poor permeability and thus drug delivery through the skin is very challenging. In this study, we examined the transdermal delivery capability of IMT-P8, a novel cell-penetrating peptide. We generated IMT-P8-GFP and IMT-P8-KLA fusion constructs and evaluated their internalization into mouse skin after topical application. Our results demonstrate that IMT-P8 is capable of transporting green fluorescent protein (GFP) and proapoptotic peptide, KLA into the skin and also in different cell lines. Interestingly, uptake of IMT-P8-GFP was considerably higher than TAT-GFP in HeLa cells. After internalization, IMT-P8-KLA got localized to the mitochondria and caused significant cell death in HeLa cells signifying an intact biological activity. Further in vivo skin penetration experiments revealed that after topical application, IMT-P8 penetrated the stratum corneum, entered into the viable epidermis and accumulated inside the hair follicles. In addition, both IMT-P8-KLA and IMT-P8-GFP internalized into the hair follicles and dermal tissue of the skin following topical application. These results suggested that IMT-P8 could be a potential candidate to be used as a topical delivery vehicle for various cosmetic and skin disease applications.
authors.affiliation: Bioinformatics Centre, CSIR-Institute of Microbial Technology, Chandigarh-160036, India.
authors.forename: Ankur
authors.initials: A
authors.lastname: Gautam
authors.affiliation: Bioinformatics Centre, CSIR-Institute of Microbial Technology, Chandigarh-160036, India.
authors.forename: Jagpreet Singh
authors.initials: JS
authors.lastname: Nanda
authors.affiliation: Bioinformatics Centre, CSIR-Institute of Microbial Technology, Chandigarh-160036, India.
authors.forename: Jesse S
authors.initials: JS
authors.lastname: Samuel
authors.affiliation: Bioinformatics Centre, CSIR-Institute of Microbial Technology, Chandigarh-160036, India.
authors.forename: Manisha
authors.initials: M
authors.lastname: Kumari
authors.affiliation: Bioinformatics Centre, CSIR-Institute of Microbial Technology, Chandigarh-160036, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Priyanka
authors.affiliation: Bioinformatics Centre, CSIR-Institute of Microbial Technology, Chandigarh-160036, India.
authors.forename: Gursimran
authors.initials: G
authors.lastname: Bedi
authors.affiliation: Department of Protein Science and Engineering, CSIR-Institute of Microbial Technology, Chandigarh-160036, India.
authors.forename: Samir K
authors.initials: SK
authors.lastname: Nath
authors.affiliation: Experimental Animal Facility, CSIR-Institute of Microbial Technology, Chandigarh-160036, India.
authors.forename: Garima
authors.initials: G
authors.lastname: Mittal
authors.affiliation: Experimental Animal Facility, CSIR-Institute of Microbial Technology, Chandigarh-160036, India.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Khatri
authors.affiliation: Bioinformatics Centre, CSIR-Institute of Microbial Technology, Chandigarh-160036, India.
authors.forename: Gajendra Pal Singh
authors.initials: GP
authors.lastname: Raghava
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001692:Biological Transport; D016923:Cell Death; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D016503:Drug Delivery Systems; D004817:Epidermis / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D018859:Hair Follicle / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000378:metabolism; D010455:Peptides / Q000235:genetics; D010539:Permeability; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*
chemical_list: D057846:Cell-Penetrating Peptides; D036341:Intercellular Signaling Peptides and Proteins; C535058:KLA peptide; D010455:Peptides; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins