Compound antimalarial ethosomal cataplasm: preparation, evaluation, and mechanism of penetration enhancement

Abstract

Malaria is still a serious public health problem in some parts of the world. The problems of recurrence and drug resistance are increasingly more serious. Thus, it is necessary to develop a novel antimalarial agent. The objectives of this study were to construct a novel compound antimalarial transdermal nanosystem–ethosomal cataplasm, to investigate its characteristics and efficiency, and to systematically explore the penetration-enhancing mechanisms of ethosomal cataplasm. Artesunate-loaded ethosomes and febrifugine-loaded ethosomes were prepared, and their characteristics were evaluated. Drug-loaded ethosomes were incorporated in the matrix of cataplasm to form the compound antimalarial ethosomal cataplasm. With the help of ethosomal technology, the accumulated permeation quantity of artesunate significantly increased at 8 hours after administration, which was 1.57 times as much as that of conventional cataplasm. Soon after administration, the ethosomal cataplasm could make a large quantity of antimalarial drug quickly penetrate through skin, then the remaining drug in the ethosomal cataplasm could be steadily released. These characteristics of ethosomal cataplasm are favorable for antimalarial drugs to kill Plasmodium spp. quickly and prevent the resurgence of Plasmodium spp. As expected, the ethosomal cataplasm showed good antimalarial efficiency in this experiment. The negative conversion rates were 100% and the recurrence rates were 0% at all dosages. The mechanism of penetration enhancement of the ethosomal cataplasm was systematically explored using an optics microscope, polarization microscope, and transmission electron microscopy. The microstructure, ultrastructure, and birefringent structure in skin were observed. Data obtained in this study showed that the application of ethosomal technology to antimalarial cataplasm could improve the transdermal delivery of drug, enhance the efficacy, and facilitate practical application in clinic.

Ethosomal nanocarriers: the impact of constituents and formulation techniques on ethosomal properties, in vivo studies, and clinical trials

“…19 In another study, addition of Tween 20 formed an unstable formulation. 27 Spans 80, 60, and 40 were not successful in producing homogeneous and stable transethosomes. 19,27 Only Span 20 was used successfully in the preparation of transethosomes of caffeine and vitamin E. 30 …”

“…Many researchers have reported superior properties of transethosomes over classical ethosomes. [17][18][19][20][21][22][23][24][25][26][27][28][29][30] Different types of edge activators and penetration enhancers have been investigated to produce ethosomal systems with better characteristics. Transethosomes were reported to entrap drugs with molecular weights ranging from 130.077 Da to 200-325 kDa.…”

“…Shen et al found that the transethosomes prepared by either Lipoid S100 or SPC50 were smaller than those produced by Lipoid E80, and the phospholipids with higher phosphatidylcholine content led to the production of stabler vesicles. 27 Highly negatively charged vesicles were produced by the incorporation of DPPG (1,2-dipalmitoyl-sn-glycero-3-phosphatidylglycerol) in the ethosomal formulation, 48 while cationic ethosomal vesicles were produced by using a cationic lipid, such as DOTAP (1,2-dioleoyl-3-trimethylammonium-propane [chloride salt]). 22 In general, the concentration range of phospholipids in an ethosomal formulation is 0.5%-5%.…”

“…The effects of Tween 80 on the ethosomal system are mainly due to its solubilizing property and the prevention of vesicle fusion. 17,19,24,27,70 Shen et al used Tween 60 in the formulation of transethosomes of artesunate and febrifugine. However, the formulations were unstable, as needle crystals formed in the formula after 5 days.…”

“…However, the formulations were unstable, as needle crystals formed in the formula after 5 days. 27 Bragagni et al introduced Tween 20 in an ethosomal system of celecoxib at 15% of the total phospholipid concentration. It was found that Tween 20-containing transethosomes had smaller vesicular size (258.4±3.3 nm), higher entrapment efficiency (54.4%), and better ex vivo skin permeation through human skin compared to transethosomes containing Tween 80 or sodium cholate.…”