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

Anna Paula Krawczyk-Santos; Ricardo Neves Marreto; Angel Concheiro; Carmen Alvarez-Lorenzo; Stephânia Fleury Taveira

doi:10.1016/j.ijpx.2022.100118

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

Int J Pharm X. 2022 May 10:4:100118. doi: 10.1016/j.ijpx.2022.100118. eCollection 2022 Dec.

Authors

Anna Paula Krawczyk-Santos¹, Ricardo Neves Marreto¹, Angel Concheiro², Carmen Alvarez-Lorenzo², Stephânia Fleury Taveira¹

Affiliations

¹ Laboratory of Nanosystems and Drug Delivery Devices (NanoSYS), School of Pharmacy, Universidade Federal de Goiás (UFG), Rua 240, Setor Leste Universitário, 74, 605-170 Goiânia, GO, Brazil.
² Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, I+DFarma Group (GI-1645), Facultad de Farmacia, iMATUS and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain.

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: CDs, cyclodextrins; GEL, Gelucire® 48/16; Mixed micelles; Nail permeation; Onychomycosis; PEG, polyethylene glycol; PPR, poly(pseudo)rotaxane; PdI, polydispersity index; Poly(pseudo)rotaxanes; RH40, Kolliphor® RH40; RH40:GEL, mixture of RH40 and GEL 1:1; Supramolecular gels; TB, terbinafine hydrochloride; Terbinafine.