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

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.

Toxicity-based toxicokinetic/toxicodynamic assessment of bioaccumulation and nanotoxicity of zerovalent iron nanoparticles in <em>Caenorhabditis elegans</em>

“…[31][32][33] Moreover, C. elegans is a well-known model and has recently been used to assess the effects of various types of nanomaterials and the pharmacological and in vivo toxic effects of drugs, implicating their importance in the field of nanomedicine. 30,34,35 There is limited information on TBTK/TD-based assessments for metal-based NP-contaminated C. elegans. However, several TBTK/TD modeling studies related to the relationships between the potential nanotoxicity of specific contaminants in C. elegans and their associated environments may provide proper methods for predicting the toxicity of nanomaterials.…”

Voltammetric determination of melatonin using a graphene-based sensor in pharmaceutical products

“…1 Moreover, melatonin is an antioxidant and free radical scavenger. 2 Melatonin is usually used in therapy for sleep disorders and jetlag. Other experimental studies have shown the effectiveness of melatonin in epilepsy, Parkinsonism, Alzheimer's disease, movement disorders, etc.…”

Hydrogen extends Caenorhabditis elegans longevity by reducing reactive oxygen species

“…After synchronization, the worms were cultured for 1 d at 20˚C. Nine worms from each group were placed in NGM plates (3 cm in diameter) containing no PQ or 0.5 mM PQ [14]. Three worms were placed per plate for a total of three plates per group.…”

“…The worms that grew to the L1 phase after the synchronization treatment were transferred to PQ (0.5 mM) medium [14]. The hydrogen group was exposed for 4 h per day.…”