Journal
JOURNAL OF CONTROLLED RELEASE
Volume 173, Issue -, Pages 67-74Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2013.10.007
Keywords
Topical; Hyaluronan; Healing; Wound; Repair; Wrinkle
Funding
- Convoy Therapeutics, Inc.
- National Science Foundation (NSF) [DGE-1144085]
- National Center for Research Resources [1S10RR022585-01A1]
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Topical penetration of macromolecules into the skin is limited by their low permeability. Here, we report the use of a skin penetrating peptide, SPACE peptide, to enhance topical delivery of a macromolecule, hyaluronic acid (HA, MW: 200-325 kDa). The peptide was conjugated to phospholipids and used to prepare an ethosomal carrier system (similar to 110 nm diameter), encapsulating HA. The SPACE-ethosomal system (SES) enhanced HA penetration into porcine skin in vitro by 7.8+/- 1.1-fold compared to PBS. The system also enhanced penetration of HA in human skin in vitro, penetrating deep into the epidermis and dermis in skin of both species. In vivo experiments performed using SKH1 hairless mice also confirmed increased dermal penetration of HA using the delivery system; a 5-fold enhancement in penetration was found compared to PBS control. Concentrations of HA in skin were about 1000-fold higher than those in blood; confirming the localized nature of HA delivery into skin. The SPACE-ethosomal delivery system provides a formulation for topical delivery of macromolecules that are otherwise difficult to deliver into the skin. (C) 2013 Elsevier B.V. All rights reserved.
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