Author(s):
Volpe-Zanutto, Fabiana ; Fonseca-Santos, Bruno [UNESP] ; McKenna, Peter E. ; Paredes, Alejandro J ; Dávila, José Luis ; McCrudden, Maelíosa T. C. ; Tangerina, Marcelo Marucci Pereira ; Ceccheto Figueiredo, Mariana ; Vilegas, Wagner [UNESP] ; Brisibe, Andi ; Akira D'vila, Marcos ; Donnelly, Ryan F. ; Chorilli, Marlus [UNESP] ; Foglio, Mary Ann
Date: 2022
Persistent ID: http://hdl.handle.net/11449/229721
Origin: Oasisbr
Subject(s): artemether; lumefantrine; malaria; surfactant-based system; transdermal
Description
Made available in DSpace on 2022-04-29T08:35:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-11-01
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® 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 µg cm-2 of ART and 94 13 µg 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.
Graduate School of Bioscience and Technology of Bioactive Products Biology Institute University at Campinas, Sao Paulo
School of Pharmacy Queen's University Belfast
UNESP- University Estadual Paulista Faculdade de Ciencias Farmaceuticas UNESP, Sao Paulo
Faculty of Pharmaceutical Science University at Campinas, Sao Paulo
Centre for Information Technology 'Renato Archer' (CTI) 3D Printing Open Lab - Laprint, Sao Paulo
Universidade de S o Paulo Departamento de Bot nica Instituto de Biociencias, Sao Paulo
Faculdade de Ciencias Médicas Universidade Estadual de Campinas, Sao Paulo
School of Mechanical Engineering University of Campinas, Sao Paulo
UNESP Univ Estadual Paulista Instituto de Biociencias, Sao Vicente
University of Calabar
UNESP- University Estadual Paulista Faculdade de Ciencias Farmaceuticas UNESP, Sao Paulo
UNESP Univ Estadual Paulista Instituto de Biociencias, Sao Vicente
