Biopartitioning micellar chromatography to predict blood to lung, blood to liver, blood to fat and blood to skin partition coefficients of drugs

Abstract

Rosemary (Rosmarinus officinalis L.) extracts (RE) are natural antioxidants that are used in food, food supplements and cosmetic applications; exert anti-inflammatory and anti-hyperglycaemic effects; and promote weight loss, which can be exploited to develop new preventive strategies against metabolic disorders. Therefore, the aim of the present study was to evaluate the preventive effects of rosemary leaf extract that was standardised to 20 % carnosic acid (RE) on weight gain, glucose levels and lipid homeostasis in mice that had begun a high-fat diet (HFD) as juveniles. The animals were given a low-fat diet, a HFD or a HFD that was supplemented with 500 mg RE/kg body weight per d (mpk). Physiological and biochemical parameters were monitored for 16 weeks. Body and epididymal fat weight in animals on the HFD that was supplemented with RE increased 69 and 79 % less than those in the HFD group. Treatment with RE was associated with increased faecal fat excretion but not with decreased food intake. The extract also reduced fasting glycaemia and plasma cholesterol levels. In addition, we evaluated the inhibitory effects of RE in vitro on pancreatic lipase and PPAR-g agonist activity; the in vitro findings correlated with our observations in the animal experiments. Thus, the present results suggest that RE that is rich in carnosic acid can be used as a preventive treatment against metabolic disorders, which merits further examination at physiological doses in randomised controlled trials.

Analytical methods for studying drug–biomembrane interactions

“…In recent years BPC has become a valid highthroughput screening platform for studying drug-membrane interaction and permeability and their correlation with biological activity and toxicity. [49][50][51] For instance, in a recent publication the phospholipidosis-inducing potential (PLIP) of 36 drugs (see Chapter 1) reported in databases was related to their IAM and electrokinetic chromatography behaviour. 52 The authors evidenced a positive, statistically signifi cant correlation between the chromatographic retention parameters of the tested pharmaceuticals and their PLIP risk.…”

The experimental and theoretical assessment of biopartitioning micellar liquid chromatography to mimic the drug‐protein binding of some pain‐relief drugs

“…BMLC speeds up screening a large number of drug candidates in partitioning process into biological systems. In recent years, BMLC has been shown good correlations with oral drug absorption, [ 26 ] partition coefficients of drugs in blood to lung, blood to liver, blood to fat and blood to skin, [ 27 ] the bioactivities of alkaloids, [ 28 ] the bioactivities of angiotensin converting enzyme inhibitors, [ 29 ] blood–brain barrier penetration ability, [ 30 ] protein binding of acidic drugs, [ 31 ] the bioactivity of cephalosporins, [ 32 ] and therapeutic efficacy parameters, preclinical pharmacology, and pharmacokinetic of phenothiazines. [ 33 ]…”

QSPR Models for Predicting Log Pliver Values for Volatile Organic Compounds Combining Statistical Methods and Domain Knowledge

“…Abraham et al [ 7 ] applied solvation equations to correlate in vitro blood-to-liver partition coefficients for VOCs and drugs. Martín-Biosca et al [ 16 ] employed biopartitioning micellar chromatography (BMC) for predicting blood-to-tissue partition coefficients of drugs and proposed PLS2 and multiple linear regression (MLR) models based on BMC retention data.…”