Novel transdermal bioadhesive surfactant-based system for release and solubility improvement of antimalarial drugs artemether-lumefantrine

Author(s):Show less -

Volpe-Zanutto, Fabiana ^{[1, 2]} ; Fonseca-Santos, Bruno ^{[3, 4]} ; McKenna, Peter E. ^[1] ; Paredes, Alejandro J. ^[1] ; Davila, Jose Luis ^[5] ; McCrudden, Maeliosa T. C. ^[1] ; Pereira Tangerina, Marcelo Marucci ^[6] ; Figueiredo, Mariana Ceccheto ^[7] ; Vilegas, Wagner ^[8] ; Brisibe, Andi ^[9] ; D'Avila, Marcos Akira ^[10] ; Donnelly, Ryan F. ^[1] ; Chorilli, Marlus ^[4] ; Foglio, Mary Ann ^[3]

Affiliation

^[1] Queens Univ Belfast, Sch Pharm, Belfast, Antrim - North Ireland

^[2] Univ Estadual Campinas, Grad Sch Biosci & Technol Bioact Prod, Biol Inst, Campinas, SP - Brazil

^[3] Univ Estadual Campinas, Fac Pharmaceut Sci, Campinas, SP - Brazil

^[4] UNESP Univ Estadual Paulista, Fac Ciencias Farmaceut, UNESP, Araraquara, SP - Brazil

^[5] Ctr Informat Technol Renato Archer CTI, 3D Printing Open Lab Laprint, Campinas, SP - Brazil

^[6] Univ Sao Paulo, Inst Biociencias, Dept Bot, Sao Paulo, SP - Brazil

^[7] Univ Estadual Campinas, Fac Ciencias Med, Campinas, SP - Brazil

^[8] UNESP Univ Estadual Paulista, Inst Biociencias, Sao Vicente, SP - Brazil

^[9] Univ Calabar, Calabar - Nigeria

^[10] Univ Estadual Campinas, Sch Mech Engn, Campinas, SP - Brazil

• Document type: Journal article
• Source: Biomedical Materials; v. 16, n. 6 NOV 1 2021.
• Web of Science Citations: 0

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 shortcomings associated 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 avoided leading to enhanced drug bioavailability in both cases. The S3AL formulation contained ART and LUM at equal concentrations (2.5% w/w of each) as well as Procetyl (R) 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 changed the system from a striae structure to a dark field structure when visualized by a polarized light microscope. Additionally, this system possessed higher viscosity and superior skin bioadhesion, as evidenced by mechanical characterization, when compared to a similar formulation containing ART alone. S3AL was also proven to be biocompatible to human keratinocyte cells. Finally, in vitro studies demonstrated the propensity of S3AL for successful delivery via the transdermal route, with 2279 +/- 295 mu g cm(-2) of ART and 94 +/- 13 mu g cm(-2) of LUM having permeated across dermatomed porcine skin after 24 h, highlighting its potential as a new candidate for the treatment of malaria. (AU)

• FAPESP's process: 16/18384-8 - Development of patches containing the association of artemether-lumefantrine for the treatment of malaria caused by Plasmodium falciparum
• Grantee: Fabiana Volpe Zanutto
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 14/16008-3 - Development of patches containing the association of artemether - lumefantrine for the treatment of malaria caused by Plasmodium falciparum
• Grantee: Fabiana Volpe Zanutto
• Support Opportunities: Scholarships in Brazil - Doctorate