Abstract
The work here described aimed to find out the location of the different species of two families of pharmaceutical substances, namely two β-blockers (atenolol and nadolol) and two benzodiazepines (midazolam and nitrazepam) in synthetic (sodium dodecyl sulphate, SDS) and natural (bile salts-sodium cholate and sodium deoxycholate) micellar aggregate solutions. Electronic spin resonance spectroscopy studies were carried out, at 25°C and at an ionic strength of 0.10M in NaCl, using 5-, 12- and 16-doxylstearic acid probes (AS). The immobilization degree of solubilized stearic acid spin probes was found to vary with the position of the nitroxide group in the sequence 5-doxylstearic acid>12-doxylstearic acid>16-doxylstearic acid for SDS and 12-doxylstearic acid>5-doxylstearic acid>16-doxylstearic acid for both bile salts investigated. Therefore, from the rotational correlational time values obtained, it can be inferred that the structure of bile salt micelles is markedly different from that of SDS micelles and the results suggest that the bile salt micelles studied have similar structure independently of differences in the molecular structure of the respective bile salts.Drug location studies were performed at pH 4.0 (SDS solutions) or 7.0 (bile salt solutions) and 10.8 in order to study the effect of the drug ionisation on its relative position on micelles. The results have shown that drug location is controlled by the (i) drug hydrophilicity and acid/base properties, with the more soluble compound in water (atenolol) exhibiting smaller variation of rotational correlational time (in SDS and bile salts solutions), and with both β-blockers exhibiting smaller deviations in the protonated forms and (ii) the bile salt monomers, with the dihydroxylic bile salt (deoxycholate) producing larger differences.The work described herein allow us to conclude that the (protonated) β-blockers are probably located on the surface of the detergent micelles, and linked to them by means of essentially electrostatic forces, while the (neutral) benzodiazepines are probably located deeper in the interior of the micelles.
Highlights
Bile acids participate in many different physiological processes
Drug location using acid probes (AS) probes was performed at pH 4.0 and pH 10.8 in order to study the effect of drug ionisation on its relative position in micellar aggregates
The analysis of the results shows that the values of rotational correlational time, τ1, of AS probe incorporated in sodium dodecyl sulphate (SDS) micelles decrease in the following order: 5-AS > 12-AS > 16-AS, which indicates a different location for the nitroxide label in the SDS aggregates
Summary
Bile acids participate in many different physiological processes. For example, the salts of these acids are involved in. Many pharmacologically active compounds are amphiphilic or hydrophobic molecules, including phenothiazines and benzodiazepine, tranquilizers, analgesics, antibiotics, tricyclic antidepressants, antihistamines, anticholinergics, -blockers, local anesthetics [19,20] These compounds may undergo different kinds of association, and their site of action in the organism is frequently the plasma membrane. Recent works include the application of spin label studies on the interactions of several compounds in heterogeneous systems, giving complementary structural information and allowing the sites of drug location in different environment (micellar or bilayer) to be draw. Three doxylstearic acid probes were used to study the location of the different species of two -blockers (atenolol and nadolol) and of two benzodiazepines (midazolam and nitrazepam) in micellar solutions of two bile salts, sodium cholate and sodium deoxycholate, and one synthetic detergent, sodium dodecyl sulphate. The paramagnetic centres of 5- and 16-doxylstearic acid spin labels are, respectively, near the micelle/water interface and deep within the micelle bilayer, and incorporation of these spin probes into micelles results in distinctive EPR spectra
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
