Caenorhabditis elegans as an alternative in vivo model to determine oral uptake, nanotoxicity, and efficacy of melatonin-loaded lipid-core nanocapsules on paraquat damage

Abstract

Mariele Feiffer Charão,1,2 Caroline Souto,2 Natália Brucker,1,2 Anelise Barth,1,2 Denise S Jornada,1,3 Daiandra Fagundez,4 Daiana Silva Ávila,4 Vera L Eifler-Lima,1,5 Silvia S Guterres,1,3 Adriana R Pohlmann,1,6 Solange Cristina Garcia1,21Post-Graduate Programme in Pharmaceutical Sciences, 2Laboratory of Toxicology (LATOX), Department of Analysis, Pharmacy Faculty, 3Department of Production and Control of Drugs, Pharmacy Faculty, Federal University of Rio Grande do Sul, Porto Alegre, 4Research Group in Biochemistry and Toxicology in Caenorhabditis elegans (GBToxCE), Federal University of Pampa – UNIPAMPA, Uruguaiana, 5Laboratory of Medical Synthesis Organic (LaSOM), Pharmacy Faculty, 6Department of Organic Chemistry, Chemistry Institute, Federal University of Rio Grande do Sul, Porto Alegre, RS, BrazilAbstract: Caenorhabditis elegans is an alternative in vivo model that is being successfully used to assess the pharmacological and toxic effects of drugs. The exponential growth of nanotechnology requires the use of alternative in vivo models to assess the toxic effects of theses nanomaterials. The use of polymeric nanocapsules has shown promising results for drug delivery. Moreover, these formulations have not been used in cases of intoxication, such as in treatment of paraquat (PQ) poisoning. Thus, the use of drugs with properties improved by nanotechnology is a promising approach to overcome the toxic effects of PQ. This research aimed to evaluate the absorption of rhodamine B-labeled melatonin (Mel)-loaded lipid-core nanocapsules (LNC) by C. elegans, the application of this model in nanotoxicology, and the protection of Mel-LNC against PQ damage. The formulations were prepared by self-assembly and characterized by particle sizing, zeta potential, drug content, and encapsulation efficiency. The results demonstrated that the formulations had narrow size distributions. Rhodamine B-labeled Mel-LNC were orally absorbed and distributed in the worms. The toxicity assessment of LNC showed a lethal dose 50% near the highest dose tested, indicating low toxicity of the nanocapsules. Moreover, pretreatment with Mel-LNC significantly increased the survival rate, reduced the reactive oxygen species, and maintained the development in C. elegans exposed to PQ compared to those worms that were either untreated or pretreated with free Mel. These results demonstrated for the first time the uptake and distribution of Mel-LNC by a nematode, and indicate that while LNC is not toxic, Mel-LNC prevents the effects of PQ poisoning. Thus, C. elegans may be an interesting alternative model to test the nanocapsules toxicity and efficacy.Keywords: C. elegans, nanotoxicology, rhodamine B-labeled polymer