Anthelmintic activity of nanoencapsulated carvacryl acetate against gastrointestinal nematodes of sheep and its toxicity in rodents.

Weibson Paz Pinheiro André,Selene Maia De Morais,Claudia Maria Leal Bevilaqua,Ana Paula Negreiros Nunes Alves,Lorena Mayana Beserra De Oliveira,Flávia Oliveira Monteiro Da Silva Abreu,José Ribamar De Paiva Junior,José Vilemar De Araújo Filho,Géssica Soares Cavalcante,Jéssica Maria Leite Dos Santos,Wesley Lyeverton Correia Ribeiro,Isaac Neto Goes Da Silva,Jomar Patrício Monteiro

doi:10.1590/s1984-29612019098

Abstract

The objective of this study was to evaluate the efficacy of carvacryl acetate (CVA) and nanoencapsulated CVA (nCVA) on gastrointestinal nematodes of sheep. The CVA was nanoencapsulated with chitosan/gum arabic and the efficacy of nanoencapsulation (EE), yield, zeta potential, nanoparticle morphology and release kinetics at pH 3 and 8 were analyzed. Acute and subchronic toxicity were evaluated in rodents and reduction of egg counts in the faeces (FECRT) of sheep. The sheep were divided into four groups (n = 10): G1, 250 mg/kg CVA; G2, 250 mg/kg nCVA; G3, polymer matrix and G4: 2.5 mg/kg monepantel. EE and nCVA yield were 65% and 57%, respectively. The morphology of the nanoparticles was spherical, size (810.6±286.7 nm), zeta potential in pH 3.2 (+18.3 mV) and the 50% release of CVA at pHs 3 and 8 occurred at 200 and 10 h, respectively. nCVA showed LD50 of 2,609 mg/kg. CVA, nCVA and monepantel reduced the number of eggs per gram of faeces (epg) by 57.7%, 51.1% and 97.7%, respectively. The epg of sheep treated with CVA and nCVA did not differ from the negative control (P>0.05). Nanoencapsulation reduced the toxicity of CVA; however, nCVA and CVA presented similar results in the FECRT.

Highlights

Gastrointestinal nematode parasitism, especially Haemonchus contortus, is one of the main limiting factors of small ruminant production worldwide because it endangers the health, welfare and productivity of sheep and goats (Araújo-Filho et al, 2018; Elmahalawy et al, 2018)
gas chromatography mass spectrometry (GC-MS) analysis identified two compounds corresponding to Carvacryl acetate (CVA) (99.3%) and carvacrol
The spectra of nanoencapsulated CVA (nCVA) presented a 1418 cm-1 (C=O symmetric stretching) band, indicating the presence of glucuronic acid in the gum arabic; 1092 cm-1 (C–O–C stretch) and 894 cm-1 bands were present in chitosan (Keawchaoon & Yoksan, 2011)

Summary

Introduction

Gastrointestinal nematode parasitism, especially Haemonchus contortus, is one of the main limiting factors of small ruminant production worldwide because it endangers the health, welfare and productivity of sheep and goats (Araújo-Filho et al, 2018; Elmahalawy et al, 2018) The control of these nematodes is performed with the administration of anthelmintics. Carvacrol is a phenolic compound found mainly in essential oils of plants of the family Lamiaceae (Besier et al, 2016) and has antiparasitic activity (Zhu et al, 2013; Shang et al, 2016; Fabbri et al, 2016) This monoterpene presents high toxicity, and acetylation is an alternative that potentiates its biological activity and increases its toxicological safety (Morais et al, 2014; Andre et al, 2016). Carvacryl acetate (CVA) showed anthelmintic activity against Schistosoma mansoni (Moraes et al, 2013), H. contortus and other sheep gastrointestinal nematodes in in vitro and in vivo assays, but the efficacy did not reach the desired therapeutic level (Andre et al, 2016)

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