Novel transdermal bioadhesive surfactant-based system for release and solubility improvement of antimalarial drugs Artemether-Lumefantrine

Fabiana Volpe-Zanutto, Bruno Fonseca-Santos, Peter E McKenna, Alejandro J. Paredes, Jose Luis Davila, Maeliosa T C McCrudden, Marcelo M. P. Tangerina, Mariana Cecchetto Figueiredo, Wagner Vilegas, Andi Brisibe, Marcos Akira d'Ávila, Ryan F Donnelly, Marlus Chorilli, Mary Ann Foglio

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Abstract

Artemether (ART) and lumefantrine (LUM) are the gold standard antimalarial drugs used for the treatment of malaria in children and pregnant women. Typically, ART and LUM are delivered orally in the form of a combined tablet, however, the appropriateness of this route of administration for these drugs is questionable due to the poor absorption and therefore bioavailability observed unless administered alongside lipid-rich foods.Transdermal drug delivery in the form of a patch-type system has been identified as a viable alternative to the conventional tablet-based therapy. A novel, surfactant-based ART-LUM formulation (S3AL), developed for transdermal delivery, may eliminate the shortcomingsassociated with oral delivery; namely poor drug absorption which is caused by the inherently low solubility of ART and LUM. Moreover, by successfully delivering these antimalarials transdermally, first-pass metabolism will be avoidedleading to enhanced drug bioavailability in both cases. The S3AL formulationcontained ART and LUMat equal concentrations (2.5% w/wof each) as well as Procetyl® AWS (30% w/w), oleic acid (10% w/w), 1-methyl-2-pyrrolidone (10% w/w), and water (45% w/w). The addition of LUM to the formulation changedthe system from a striae structure toa dark field structure when visualized bya polarised light microscope. Additionally,this system possessedhigher viscosity and superior skin bioadhesion,as evidenced by mechanical characterisation, when compared to a similar formulation containing ARTalone. S3AL was also proven to be biocompatible to human keratinocyte cells (HaCaT). Finally, in vitro studies demonstrated the propensity of S3AL for successful delivery via the transdermal route, with 2279 ± 295 µg/cm2 of ART and 94 ± 13 µg/cm2 of LUM having permeated across dermatomed porcine skin after 24 h, highlighting its potential as a new candidate for the treatment of malaria.
Original languageEnglish
Article number065015
JournalBiomedical Materials
Volume16
Early online date04 Oct 2021
DOIs
Publication statusEarly online date - 04 Oct 2021

Keywords

  • artemether
  • lumefantrine
  • malaria
  • surfactant-based system
  • transdermal

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