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.
Highlights
Delivery of therapeutic molecules through the skin is gaining tremendous scientific attention over the years
A few studies have shown that small peptides such as TAT20, polyarginine[21], meganin[22], penetratin[23], TD-124 and SPACE-peptide[25] can penetrate the skin’s protective barriers to get to the deeper layers and enhance the transdermal delivery of various therapeutic molecules like siRNA26, 1Bioinformatics Centre, CSIR-Institute of Microbial Technology, Chandigarh-160036, India. 2Department of Protein Science and Engineering, CSIR-Institute of Microbial Technology, Chandigarh-160036, India. 3Experimental Animal Facility, CSIR-Institute of Microbial Technology, Chandigarh-160036, India
We recently identified and characterized a novel human protein-derived arginine-rich cell-penetrating peptides (CPPs), IMT-P8 (IMT-P8; Institute of Microbial Technology-Peptide 8)[28] using in silico prediction algorithm, CellPPD29 and followed by experimental validation
Summary
Delivery of therapeutic molecules through the skin is gaining tremendous scientific attention over the years. Peptides have been emerged as safer alternatives to enhance the delivery of small and large molecules into and across the skin[12] In this context, transdermal delivery of therapeutics using cell-penetrating peptides (CPPs) is an attractive and novel approach[11]. A few studies have shown that small peptides such as TAT20, polyarginine[21], meganin[22], penetratin[23], TD-124 and SPACE-peptide[25] can penetrate the skin’s protective barriers to get to the deeper layers and enhance the transdermal delivery of various therapeutic molecules like siRNA26, www.nature.com/scientificreports/. Before performing experiments on mouse skin for topical delivery, we first examined the delivery of cargoes using IMT-P8 on continuously growing human cells These in vitro experiments confirmed that IMT-P8 is capable of delivering cargoes (FITC, peptide and protein) into variety of human cells. Our results demonstrate that IMT-P8 facilitates the delivery of GFP and KLA into mouse skin and in different human tumor cells at very low concentration suggesting that IMT-P8 might be beneficial for the treatment of local skin infections and various cosmetic applications
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.