Therapeutic Efficacy of Carvacrol-Loaded Nanoemulsion in a Mouse Model of Schistosomiasis

Abstract

Since praziquantel is the only drug available to treat schistosomiasis, a neglected parasitic disease that affects more than 240 million people worldwide, there is an urgent demand for new antischistosomal agents. Natural compound-loaded nanoparticles have recently emerged as a promising alternative for the treatment of schistosomiasis. Carvacrol is an antimicrobial monoterpene present in the essential oil extracted from several plants, especially oregano (Origanum vulgare). In this study, a carvacrol nanoemulsion (CVNE) was prepared, characterized, and administered orally (200 mg/kg) in a mouse infected with either immature (prepatent infection) or adult (patent infection) Schistosoma mansoni. For comparison, data obtained with an unloaded nanoemulsion (blank formulation), free carvacrol, and the drug of reference praziquantel are also presented. CVNE was more effective than free carvacrol in reducing the worm burden and egg production in both patent and prepatent infections. Favorably, CVNE had a high effect in terms of reducing the number of worms and eggs (85%-90%) compared with praziquantel (∼30%) in prepatent infection. In tandem, carvacrol-loaded nanoemulsion markedly improved antischistosomal activity, showing efficiency in reducing worm and egg burden, and thus it may be a promising delivery system for the treatment of schistosomiasis.

Keywords: antischistosomal compounds; drug delivery; infectious diseases; nanoemulsion; nanotechnology; natural product.

FIGURE 1

Chemical structure and droplet size distributions. (A) Chemical structure of carvacrol. (B) Carvacrol nanoemulsion droplet size distribution curve by intensity after 1 day of formulation (C) Carvacrol nanoemulsion droplet size distribution curve by intensity after 90 days of formulation.

FIGURE 2

Efficacy of carvacrol nanoemulsion (CVNE), blank nanoemulsion (BNE), free carvacrol, and praziquantel (PZQ) in mice harboring prepatent Schistosoma mansoni infection. (A) Effect of compounds on worm burden. (B) Effect of compounds on egg burden. Drugs were administered orally using a single dose of 200 mg/kg (CVNE and free carvacol) or 400 mg/kg (PZQ) 21 days post-infection to mice harboring juvenile S. mansoni. Groups of S. mansoni-infected control were given a corresponding amount of vehicle on the same timetable. Points represent data from individual mice (n = 5 per group). The percentages of reduction in worms and egg burden are in parentheses. Horizontal bars represent median values. *p < 0.05 and ****p < 0.0001 compared with infected untreated control.

FIGURE 3

Efficacy of carvacrol nanoemulsion (CVNE), blank nanoemulsion (BNE), free carvacrol, and praziquantel (PZQ) in mice harboring patent Schistosoma mansoni infection. (A) Effect of compounds on worm burden. (B) Effect of compounds on egg burden. Drugs were administered orally using a single dose of 200 mg/kg (CVNE and free carvacrol) or 400 mg/kg (PZQ) 42 days post-infection to mice harboring adult S. mansoni. Groups of S. mansoni-infected control were given a corresponding amount of vehicle on the same timetable. Points represent data from individual mice (n = 5 per group). The percentages of reduction in worms and egg burden are in parentheses. Horizontal bars represent median values. *p < 0.05, ****p < 0.0001 compared with infected untreated control.