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 IILC), 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 5 Å. 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 IILC-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.