Poly(pseudo)rotaxanes formed by mixed micelles and α-cyclodextrin enhance terbinafine nail permeation to deeper layers

Abstract

This work aimed to develop water-based formulations for onychomycosis topical treatment using micelles of small pegylated surfactants associated with α-cyclodextrin (αCD) to deliver terbinafine to the nail. Kolliphor® RH40 (RH40) and Gelucire® 48/16 (GEL) single and mixed micelles (RH40:GEL 1:1) were prepared. αCD was added to the surfactants dispersions to form poly(pseudo)rotaxanes (PPR). Formulations were characterized in terms of drug solubilization (3 to 34-fold increase), particle size (9–11 nm) and Z-potential (+0.3 − +1.96 mV), blood compatibility (non-hemolytic), rheological behavior (solid-like viscoelastic properties after 5–10% αCD addition), drug release and interaction with the nail plate. GEL micelles and surfactant-10% αCD PPRs notably hydrated the nail plate. The high viscosity of PPR led to a slower drug release, except for RH40:GEL +10% αCD that surprisingly released terbinafine faster. The RH40:GEL +10% αCD formulation delivered twice more amount of terbinafine to deeper regions of nail plate compared to other formulations. The results evidenced the potential of PPR formed by small pegylated surfactants as a water-based formulation for nail drug delivery.

Keywords

• Mixed micelles
• Poly(pseudo)rotaxanes
• Supramolecular gels
• Nail permeation
• Terbinafine
• Onychomycosis