title: Superiority of liquid crystalline cubic nanocarriers as hormonal transdermal vehicle: comparative human skin permeation-supported evidence.
abstract: The aim of this investigation was to explore the feasibility of various nanocarriers to enhance progesterone penetration via the human abdominal skin.
  
  
  
  Four progesterone-loaded nanocarriers; cubosomes, nanoliposomes, nanoemulsions and nanomicelles were formulated and characterized regarding particle size, zeta potential, % drug encapsulation and in vitro release. Structural elucidation of each nanoplatform was performed using transmission electron microscopy. Ex vivo skin permeation, deposition ability and histopathological examination were evaluated using Franz diffusion cells.
  
  
  
  Each nanocarrier was fabricated with a negative surface, nanometric size (≤ 270 nm), narrow size distribution and reasonable encapsulation efficiency. In vitro progesterone release showed a sustained release pattern for 24 h following a non-Fickian transport diffusion mechanism. All nanocarriers exhibited higher transdermal flux relative to free progesterone. Cubosomes revealed a higher skin penetration with transdermal steady flux of 48.57.10(-2) ± 0.7 µg/cm(2) h. Nanoliposomes offered a higher percentage of skin progesterone deposition compared to other nanocarriers. Based on the histopathological examination, cubosomes and nanoliposomes were found to be biocompatible for transdermal application. Confocal laser scanning microscopy confirmed the ability of fluoro-labeled cubosomes to penetrate through the whole skin layers.
  
  
  
  The elaborated cubosomes proved to be a promising non-invasive nanocarrier for transdermal hormonal delivery.
authors.affiliation: a Department of Industrial Pharmacy, Faculty of Pharmacy , Alexandria University , Alexandria , Egypt.
authors.forename: Salma M
authors.initials: SM
authors.lastname: Mohyeldin
authors.affiliation: a Department of Industrial Pharmacy, Faculty of Pharmacy , Alexandria University , Alexandria , Egypt.
authors.forename: Mohammed M
authors.initials: MM
authors.lastname: Mehanna
authors.affiliation: a Department of Industrial Pharmacy, Faculty of Pharmacy , Alexandria University , Alexandria , Egypt.
authors.forename: Nazik A
authors.initials: NA
authors.lastname: Elgindy
mesh_terms: D000279:Administration, Cutaneous; D002626:Chemistry, Pharmaceutical; D004058:Diffusion; D005260:Female; D006801:Humans; D050866:Liquid Crystals / Q000737:chemistry*; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption
keywords: Nanocarriers; cubosomes; human skin; progesterone; transdermal permeation