Brain Tissue Binding Assay

In recent years, evaluating the efficiency of drug delivery to the central nervous system (CNS) in vitro has become an essential step before drug clinical testing and in vivo experiments, and is also the basis for molecular pharmacokinetics and drug efficacy studies. This data represents and predicts that the candidate drug can reach its pharmacological target at an effective dose, and at an effective concentration to elicit the desired pharmacological effect. The prediction of drug delivery capacity is usually considered through two aspects, one is to measure the rate of drug delivery to the nervous system and the speed at which the compound crosses the blood-brain barrier, and the other is the balance of the drug in the CNS, which is the concentration ratio of tissue-bound and free drug in plasma or brain tissue. Creative Biolabs here provides you with efficient and stable brain tissue binding assays to help you better understand the brain drug delivery process and its impact on drug action through our stable and reproducible experimental data.

Tissue Binding and Free Drug Hypothesis

According to the free drug hypothesis, only free drugs can reach the target tissue through passive diffusion through the membrane, and only free drugs near the target tissue can react with them to exert their curative effect, and only unbound drugs can undergo subsequent metabolism and excretion processes. Brain tissue proteins can affect drug's steady-state volume of distribution and drug half-life by binding to them, thereby affecting the therapeutic achievements and reducing curative effect. Assays for the ability of a drug to bind tissue contribute to:

1. Predict in vivo drug clearance
2. Determinate of human dose
3. Predict cross-species comparison results
4. Determine disease state
5. Identify potential pharmacological and toxicological effects

There are many approaches available for estimating the binding capacity of drugs and brain tissue, which are usually expressed as the ratio of the amounts of free drugs divided by the total volume within brain tissue. Commonly used in vitro methods include high-throughput equilibrium dialysis and brain slicing.

Fig 1. Maximum whole (A) and free (B) concentrations of male mice after IV dosing. (Dow, et al., 2011)

Our Brain Tissue Binding Assay Service

The value of many promising CNS drug candidates is diminished after entering and binding the brain tissue, so the detection of brain tissue binding during drug development would be beneficial for drug curative effect prediction. Creative Biolabs can perform brain tissue binding assays for you by common means, such as equilibrium dialysis of brain homogenates and buffered brain slices, saving you from complicated and time-consuming work, providing you with stable and reproducible results, and avoiding the false estimates of drug efficiency resulting from experimental design and manipulation. If you have any needs, please do not hesitate to contact us so that our professional team assists you in overcoming this major hurdle in drug development and pharmacology research.

Reference

1. Dow, G.S.; et al. Central nervous system exposure of next generation quinoline methanols is reduced relative to mefloquine after intravenous dosing in mice. Malaria Journal. 2011, 10: 150.