title: Enhanced cutaneous bioavailability of dehydroepiandrosterone mediated by nano-encapsulation.
abstract: Polymeric nanocarriers, especially nanospheres (NSs) and nanocapsules (NCs), can promote the penetration of their cargo through the skin barrier, towards improved cutaneous bioavailability. Dehydroepiandrosterone (DHEA), an endogenous hormone exhibiting poor aqueous solubility, was shown to be effective in modulating skin-aging processes following topical application. In this study, we designed adequate DHEA preparations, in an attempt to enable local delivery of the active ingredient to the viable skin layers. In addition, the potential efficiency of DHEA NCs on dermal collagen synthesis was evaluated. Cryo-TEM observations and thermal analysis indicated that DHEA was successfully incorporated within a stable NC-based delivery system. Moreover, higher [(3)H]-DHEA levels were recorded in the viable skin layers following different incubation periods of NCs on excised pig skin specimens as compared to DHEA oil solution (free molecule). Furthermore, significantly higher (4-fold) skin flux values were observed for the DHEA NCs as compared to the values elicited by the oil control solution. Finally, collagen synthesis in human skin organ culture, assessed by the incorporation of [(3)H]-proline, was up to 42% higher for DHEA NCs 48h post-topical application than for the untreated specimens. Overall, these results suggest that poly lactic-co-glycolic acid (PLGA)-based NCs have promising potential to be used topically for various skin disorders.
authors: Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
authors: Amit
authors: A
authors: Badihi
authors: Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
authors: Nir
authors: N
authors: Debotton
authors: Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
authors: Marina
authors: M
authors: Frušić-Zlotkin
authors: Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
authors: Yoram
authors: Y
authors: Soroka
authors: Department of Cosmetic Surgery, Hadassah Hospital Ein Kerem, Jerusalem 9112102, Israel.
authors: Rami
authors: R
authors: Neuman
authors: Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel. Electronic address: benita@cc.huji.ac.il.
authors: Simon
authors: S
authors: Benita
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001682:Biological Availability; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000008:administration & dosage; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry; D054118:Nanospheres / Q000008:administration & dosage* / Q000737:chemistry; D011100:Polyglycolic Acid / Q000008:administration & dosage; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D013552:Swine
chemical_list: D053769:Nanocapsules; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003687:Dehydroepiandrosterone; D003094:Collagen
keywords: Collagen; DHEA; Nanocapsules; PLGA; Permeation; Skin