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

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® 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.

Pioneer Use of Antimalarial Transdermal Combination Therapy in Rodent Malaria Model

“…Many new antimalarial combination therapy studies have been reported towards the goal of overcoming ACT-resistant P. falciparum , including derivatives of artemisinin with other compounds, but despite these efforts, the resistance of P. falciparum to ACT remains increasing in prevalence [ 18 , 19 ]. Antimalarial drug development studies for children using artemisinin derivatives were also reported [ 20 , 21 ].…”

Vertical Alignment of Liquid Crystal on Sustainable 2,4-Di-tert-butylphenoxymethyl-Substituted Polystyrene Films

“…Lyotropic LCs (or lyomesophases) consisting of amphiphiles have a tendency to form self-assembled structures depending on their concentration in solution. The physicochemical properties of lyotropic LCs and their intrinsic structures, including lamellar, hexagonal, and cubic phases, make them suitable as drug delivery agents in pharmaceutical sciences in a wide range of applications [ 11 , 12 , 13 , 14 , 15 , 16 ]. In particular, the hexagonal and cubic phases are of high interest in the field of drug delivery agents owing to their ability to control or maintain the release of hydrophilic and hydrophobic drug molecules with a wide range of molecular weights [ 17 , 18 , 19 ].…”