Drug Absorption Efficiency in Caenorhbditis elegans Delivered by Different Methods

Abstract

Background Caenorhbditis elegans has being vigorously used as a model organism in many research fields and often accompanied by administrating with various drugs. The methods of delivering drugs to worms are varied from one study to another, which make difficult in comparing results between studies.Methodology/Principal FindingsWe evaluated the drug absorption efficiency in C. elegans using five frequently used methods with resveratrol with low aqueous solubility and water-soluble 5-Fluoro-2′-deoxyuridine (FUDR) as positive compounds. The drugs were either applied to the LB medium with bacteria OP50, before spreading onto Nematode Growth Medium (NGM) plates (LB medium method), or to the NGM with live (NGM live method) or dead bacteria (NGM dead method), or spotting the drug solution to the surface of plates directly (spot dead method), or growing the worms in liquid medium (liquid growing method). The concentration of resveratrol and FUDR increased gradually within C. elegans and reached the highest during 12 hours to one day and then decreased slowly. At the same time point, the higher the drug concentration, the higher the metabolism rate. The drug concentrations in worms fed with dead bacteria were higher than with live bacteria at the same time point. Consistently, the drug concentration in medium with live bacteria decreased much faster than in medium with dead bacteria, reach to about half of the original concentration within 12 hours.ConclusionResveratrol with low aqueous solubility and water-soluble FUDR have the same absorption and metabolism pattern. The drug metabolism rate in worms was both dosage and time dependent. NGM dead method and liquid growing method achieved the best absorption efficiency in worms. The drug concentration within worms was comparable with that in mice, providing a bridge for dose translation from worms to mammals.

High-Content Microfluidic Screening Platform Used To Identify σ2R/Tmem97 Binding Ligands that Reduce Age-Dependent Neurodegeneration in C. elegans SC_APP Model

“…This result is encouraging in light of a recent study reporting that drug uptake by C. elegans is comparable to that of mice, especially when they are treated in a LC environment. 78 Moreover, our recent study with SAS-0132 has demonstrated an improvement in cognitive performance in transgenic AD mice. 8 Finally, the dose-dependent variations observed even within this small compound collection show that our microfluidic screening technology is an excellent platform for assessing structure–activity-relationships.…”

Role of CYP eicosanoids in the regulation of pharyngeal pumping and food uptake in Caenorhabditis elegans

“…This applies even more in the light of an encapsulated pharynx, isolated from the rest of the worm by a specialized basal lamina. Moreover, recent investigations revealed that the more economic approach of spotting compounds on the agar surface achieved lower absorption effi ciency in worms when compared with other drug delivering methods, as pouring compounds together with agar ( 38 ). In the case of the spot method, the solution will immerse into the NGM agar, which reduces the availability.…”

C. elegans in high-throughput drug discovery

“…For these reasons, higher initial compound concentrations (25–100 µM) are typically used in C. elegans -based drug screens. A recent study, however, suggests that drug uptake by C. elegans is comparable to that of mice [51]. The study also found that culture and assay methods - liquid vs agar-based cultures, E. coli preparation and when and how the drugs were added – had significant effects on drug efficacy.…”

“…The study also found that culture and assay methods - liquid vs agar-based cultures, E. coli preparation and when and how the drugs were added – had significant effects on drug efficacy. The use of heat-killed, rather than live E. coli increased the uptake of drugs as measured by higher internal drug concentrations [51]. The killing of E. coli presumably prevented drug metabolism by the bacteria which in turn increased drug availability [51].…”

“…The use of heat-killed, rather than live E. coli increased the uptake of drugs as measured by higher internal drug concentrations [51]. The killing of E. coli presumably prevented drug metabolism by the bacteria which in turn increased drug availability [51]. These factors should be weighed carefully in the assay development, in order to optimize drug delivery.…”