title: H(II) mesophase and peptide cell-penetrating enhancers for improved transdermal delivery of sodium diclofenac.
abstract: This study develops a novel transdermal delivery vehicle for the enhanced delivery of sodium diclofenac (Na-DFC). The system utilizes the advantages of reversed hexagonal lyotropic liquid crystals (H(II)LC), combined with a peptide cell penetration enhancer (CPE), creating together an adaptable system that provides versatile options in the field of transdermal delivery. This enhancer peptide is based on a family of amphipatic peptides that exhibit improved membrane permeability. Franz permeation cell experiments revealed that the peptide enhancer (RALA) improved Na-DFC skin penetration of the liquid crystal 2.2-fold. We studied the structural effects of RALA solubilization on the H(II) mesophase. RALA acts as a chaotropic agent, interfering in the structure of the water, and causes a measurable swelling of the aqueous cylinders by 5A. Small angle X-ray scattering (SAXS) and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) measurements reveal enhanced hydration of the glycerol monooleate (GMO) headgroups and a 6.5% increase in the fraction of non-freezable water resulting from RALA incorporation. RALA caused a gradual increase in the GMO effective headgroup area due to the hydration, leading eventually to a transform of the hexagonal structure towards a lamellar one. Circular dichroism and ATR-FTIR measurements showed a conservation of the peptide structure when incorporated into the H(II) mesophase. The combined H(II)LC-CPE systems can serve as high potential vehicles for a variety of drugs, as they can easily be modified by varying the composition and temperature, according to the required dose and delivery features.
authors.affiliation: Casali Institute of Applied Chemistry, The Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 91904, Israel.
authors.forename: Marganit
authors.initials: M
authors.lastname: Cohen-Avrahami
authors.forename: Abraham
authors.initials: A
authors.lastname: Aserin
authors.forename: Nissim
authors.initials: N
authors.lastname: Garti
mesh_terms: D000042:Absorption; D000279:Administration, Cutaneous; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002942:Circular Dichroism; D004008:Diclofenac / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D005989:Glycerides / Q000737:chemistry; D050866:Liquid Crystals; D008853:Microscopy / Q000379:methods; D016011:Normal Distribution; D010455:Peptides / Q000737:chemistry*; D012542:Scattering, Radiation; D012867:Skin / Q000187:drug effects*; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature
chemical_list: D005989:Glycerides; D010455:Peptides; D004008:Diclofenac; C005953:monoolein