H2020Индивидуална стипендия2018–2020

ChromaFish · Chromatographic micro-column development for pharmaceutical applications in zebraFish

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2018-06-01 → 2020-09-15
Финансиране от ЕС: 160 800 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Разработват се нови микроколони и методи за измерване на това как лекарствата за централната нервна система проникват в мозъка на зебрарибите. Това помага за по-точното проследяване на разпределението на лекарствата в организма и намалява нуждата от тестове с мишки и плъхове.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Chromatographic micro-column development for pharmaceutical applications in zebraFish

The drugs targeting the central nervous system have to reach their interaction sites, which is complicated by the presence of the blood-brain barrier, a selective semipermeable membrane separating the circulating blood from the brain and extracellular fluid. To predict Absorption, Distribution, Metabolism and Excretion properties (ADME), and more specifically absorption and permeability, high throughput screening is the method of choice. Predictive in silico and in vitro models have been developed but the outcome should be confirmed by in vivo models. Murine and rat models are well established but zebrafish can be an attractive alternative that address the increasing ethical concerns about animal testing. They are less care-intensive, possess a high genetic, physiologic and pharmacologic homology to humans, and their high fecundity and small size allow to perform “in vitro-like” screenings in well plates using very few amount of drugs. A novel sample preparation and analytical method to measure the whole-body uptake of drugs in zebrafish was developed in the laboratory [1]. The next step was to study uptake and metabolism of new drugs in the brain, where infinite small concentrations are expected. The aim was to develop a new type of capillary columns with core-shell particles and inner diameters < 300 µm. Combined with mass spectrometry, it would enhance the sensitivity and in this way lead to lower limits of quantification. The second objective was to develop a novel brain dissection technique and investigate the activity of transporter proteins. Once a suitable and validated analytical methodology would be in place, it could be applied to new drug candidates, and the results compared with those obtained using more traditional in vivo models. [1] Kislyuk S. et al. Talanta, 780–788

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

ADME (Absorption, Distribution, Metabolism and Excretion) studies focus on the examination and prediction of drug behavior in the human body. Zebrafish present a good in vivo model for this purpose since they comply with the 3R principle of humane animal research (Replacement, Reduction and Refinement). The research group of Prof. Deirdre Cabooter recently developed a novel sample preparation and analytical method to accurately measure the whole-body uptake of drugs in zebrafish. The next step is to further exploit the developed methodology to study other aspects of ADME, in particular uptake and metabolisation of new drug candidates in the brain. Since the blood-brain barrier is a major obstacle preventing many pharmaceuticals from achieving effective concentrations in the brain, infinite small concentrations are to be expected. The detection of low brain concentrations can be improved by using advanced analytical techniques with lower sample dilution and thus enhanced detection limits. An important part of this research project will therefore be devoted to the development and characterization of new capillary column formats based on core-shell particles offering unprecedented sensitivity and unique selectivities. A new brain dissection technique will moreover be developed to isolate the brain from the circulating blood and investigate the uptake and metabolisation of selected pharmaceuticals in the brain. Molecular transport routes will be unraveled and the uptake in specific parts of the brain will be investigated as well using laser microdissection microscopy. Finally, the potential of the developed methodology to provide a robust protocol for brain uptake measurements in industrial applications will be investigated by comparing the outcome obtained by zebrafish experiments with typical results obtained by more traditional models (murine, rat).

Оригинален текст от CORDIS (на английски).

Участници

KATHOLIEKE UNIVERSITEIT LEUVEN · LeuvenКоординаторБелгия