Determination of Aggregation Numbers of Bile Salt Micelles with the Depression of the Solution Freezing Point

The special geometry of the steroid skeleton causes formation of bile acid anion micelles with small aggregation numbers, in contrast to aliphatic amphiphiles. Relative to the tendency to reduce membrane toxicity, pharmacological investigations of bile acids are mainly concerned with their oxo derivatives. Since micelles of these bile acids have been insufficiently studied, the objective of this work is the determination of aggregation numbers of corresponding micelle monomers. The aggregation numbers were determined using the freezing point depression of the solutions by applying the appropriate equations of Debye-Hückel, Guggenheim and Gibbs-Duhems, and using pNa data measured with a Na-selective electrode. Depending on the structure of the bile acid anion, the values obtained for the aggregation numbers were in the range from 2.09 to 3.44. The increase in number of oxo groups in the molecule is accompanied by a decrease in hydrophobicity of the convex side of the steroid skeleton of the bile acid anion, resulting in a lower aggregation number

Influence of bile acids on drug transportation processes in vitro

U ovoj disertaciji su ispitivani efekti žučnih kiselina na transportne procese kod kojih se ispoljava efekat građenja molekulskih agregata (micele, mešovite micele, kompleks sa vodoničnim vezama itd). Ispitan je uticaj temperature na kritičnu micelarnu koncnentraciju holne, deoksiholne i henodeoksiholnekiseline i njihovih keto derivata, određena je entropija formiranja micele, koja je važan parametar ne samo u samoasocijaciji žučnih kiselina već i u njihovoj interakciji sa hidrofobnim molekulima. Određen je kompleks sa vodoničnim vezama izmeđ u lidokaina i žučnih kiselina, regresiona jednačina koja povezuje strukturne parametre žučnih kiselina i ravnotežnu konstantu formiranja tog kompleksa. Zatim je ispitivano delovanje žučnih kiselina u hloroformu na kinetiku prelaza lidokaina i verapamila iz vodene faze u hloroform (model za predtretman sa žučnim kiselinama) U ovom radu je određena i solubilizacija lecitina i holesterola sa žučnim kiselinama.In this work,  effects of bile acids which form molecular  aggregates (micelles, mixed micelles, hydrogen complex etc.) on transportation processes were investigated. Influence of temperature on critical micellar concentration of cholic, deoxyholic and henodeoxycholic acids and its keto derivatives was  examined. Also, micelle formation entropy was determined. This is very important parameter for self-association of bile acids and their interactions with hydrophobic molecules. Hydrogen complex of lidocain and bile acids was investigated and regression equation which connects structural parameters of bile acids  and equilibrium constant of forming this complex was established. After that, effects of bile acids on transfer kinetics of lidocaine and verapamil from aqueous phase to chlorophorm was investigated. Also, micellar solubilization of lecithin and cholesterolby bile acids was determined

Interaction between triton X100 and BRIJ 58 in their binary mixed micelles

The micellization of the binary mixture of surfactants Triton X100 – Brij 58 in an aqueous solution was investigated using a spectrofluorimetric method with pyrene as a probe molecule. There are synergistic interactions between the micellar building units in the binary mixed micelles Triton X100 – Brij 58, which increase with increasing temperature. The analyzed binary mixed micelles possess molar excess entropy

Conductometric study of sodium dodecyl sulfate - nonionic surfactant (Triton X-100, Tween 20, Tween 60, Tween 80 or Tween 85) mixed micelles in aqueous solution

The present study is concerned with the determination of the critical micelle concentration (cmc) of mixed micelles of sodium dodecyl sulfate with one of five nonionic surfactants (Triton X-100, Tween 20, Tween 60, Tween 80 or Tween 85) from conductance measurements. Based on the calculated values of the β parameters we have noticed that SDS-nonionic surfactants mostly showed strong synergistic effect. It was found that nonionic surfactants with mainly longer and more hydrophobic tail show stronger interactions with hydrophobic part of SDS, thus expressing stronger synergism. In SDS-Tween 80 binary system the strongest synergistic effect was noticed. SDS-Tween 85 micellar system showed antagonistic effect, most probably because the presence of the double bond in its three hydrophobic tails (three C18 tails) makes it sterically rigid

Application of a widely-used tropical anti-worm agent, mebendazole, in modern oncology

Although clinical trials have not been completed, it has already been confirmed that mebendazole, a well-known anti-parasitic drug widely used in the tropical areas, inhibits cancer cell growth. Preclinical studies show that mebendazole notably impedes the growth of malignant and metastatic tumors such as osteosarcoma and soft tissue sarcoma, melanoma, carcinoma (lung, colorectal, breast, ovarian, hepatocellular and adrenocortical), acute myeloid leukaemia, glioblastoma multiforme and  meduloblastoma. Mebendazole can induce the depolymerization of microtubules in neoplasms and newly formed vasculature, stopping tumor growth and neoangiogenesis, along with other proposed mechanisms of action.Keywords: Anthelmintic, Mebendazole, Cancer treatment, Antimicrotubullar effect, Antineoangiogenesi

Interactions between selected bile salts and Triton X-100 or sodium lauryl ether sulfate

<p>Abstract</p> <p>Background</p> <p>In order to develop colloidal drug carriers with desired properties, it is important to determine physico-chemical characteristics of these systems. Bile salt mixed micelles are extensively studied as novel drug delivery systems. The objective of the present investigation is to develop and characterize mixed micelles of nonionic (Triton X-100) or anionic (sodium lauryl ether sulfate) surfactant having oxyethylene groups in the polar head and following bile salts: cholate, deoxycholate and 7-oxodeoxycholate.</p> <p>Results</p> <p>The micellization behaviour of binary anionic-nonionic and anionic-anionic surfactant mixtures was investigated by conductivity and surface tension measurements. The results of the study have been analyzed using Clint's, Rubingh's, and Motomura's theories for mixed binary systems. The negative values of the interaction parameter indicate synergism between micelle building units. It was noticed that Triton X-100 and sodium lauryl ether sulfate generate the weakest synergistic interactions with sodium deoxycholate, while 7-oxodeoxycholate creates the strongest attractive interaction with investigated co-surfactants.</p> <p>Conclusion</p> <p>It was concluded that increased synergistic interactions can be attributed to the larger number of hydrophilic groups at α side of the bile salts. Additionally, 7-oxo group of 7-oxodeoxycholate enhance attractive interactions with selected co-surfactants more than 7-hydroxyl group of sodium cholate.</p

Influence of bile acids on drug transportation processes in vitro

U ovoj disertaciji su ispitivani efekti žučnih kiselina na transportne procese kod kojih se ispoljava efekat građenja molekulskih agregata (micele, mešovite micele, kompleks sa vodoničnim vezama itd). Ispitan je uticaj temperature na kritičnu micelarnu koncnentraciju holne, deoksiholne i henodeoksiholnekiseline i njihovih keto derivata, određena je entropija formiranja micele, koja je važan parametar ne samo u samoasocijaciji žučnih kiselina već i u njihovoj interakciji sa hidrofobnim molekulima. Određen je kompleks sa vodoničnim vezama izmeđ u lidokaina i žučnih kiselina, regresiona jednačina koja povezuje strukturne parametre žučnih kiselina i ravnotežnu konstantu formiranja tog kompleksa. Zatim je ispitivano delovanje žučnih kiselina u hloroformu na kinetiku prelaza lidokaina i verapamila iz vodene faze u hloroform (model za predtretman sa žučnim kiselinama) U ovom radu je određena i solubilizacija lecitina i holesterola sa žučnim kiselinama.In this work,  effects of bile acids which form molecular  aggregates (micelles, mixed micelles, hydrogen complex etc.) on transportation processes were investigated. Influence of temperature on critical micellar concentration of cholic, deoxyholic and henodeoxycholic acids and its keto derivatives was  examined. Also, micelle formation entropy was determined. This is very important parameter for self-association of bile acids and their interactions with hydrophobic molecules. Hydrogen complex of lidocain and bile acids was investigated and regression equation which connects structural parameters of bile acids  and equilibrium constant of forming this complex was established. After that, effects of bile acids on transfer kinetics of lidocaine and verapamil from aqueous phase to chlorophorm was investigated. Also, micellar solubilization of lecithin and cholesterolby bile acids was determined

Symmetry (Asymmetry) of the Molar Excess Gibbs Free Energy Function of the Binary Mixed Micelles of Bile Acid Anion and Classical Cationic Surfactant: Influence of Sterically Shielded and Sterically Unshielded Polar Groups of the Steroid Skeleton

Binary mixtures of surfactants build a binary mixed micelle in which the ratio of surfactants usually differs from the initial ratio of surfactants in their binary mixture. The thermodynamic stabilization of the binary mixed micellar pseudophase about the hypothetical ideal state (intermolecular interactions between the different particles and the conformational states of the particles are identical to those of monocomponent states) is described by the molar excess Gibbs free energy (gE). The dependence of gE on the molar fraction of surfactant i (xi) from the binary mixed micelle can be described by a symmetric function (symmetry is described to the line parallel to the y-axis and passes through xi = 0.5) or by an asymmetric function. Theoretical analysis (canonical partition function, conformational analysis) examines how the presence of different polar functional groups, some of which are sterically shielded from the steroid skeleton of bile salts (surfactant), affect the symmetry of the function gE of the binary mixed micelle of the cholic acid anion (bile salts) and classic cationic surfactant (hydrophobic tail and polar head). Suppose the steroid skeleton of the bile salt contains non-sterically shielded polar groups (or the temperature is relatively high). In that case, gE is a symmetric function. At the same time, if the steroid skeleton also contains sterically shielded polar groups, then the gE function is asymmetric

A contribution to the study of hydrophobicity (lipophilicity) of bile acids with an emphasis on oxo derivatives of 5β-cholanoic acid

Due to their promotory action on the transport of some drugs through various membranes (lipophilic barriers), oxo derivatives of bile acids have recently been increasingly used in biopharmacy. These compounds exhibit also a lower membranolytic (toxic) activity than their hydroxy analogues. Because of that it is of special importance to find out the descriptors that would adequately describe the structure of bile acids and their biological activity and be used to model the quantitative structure-activity relationship. In view of this, the present work is concerned with the application of the chromatographic parameter RM0 obtained by normal-phase thin-layer chromatography in the solvent system toluene-butanol and silica gel as stationary phase to describe the lipophilicity of bile acids. Also, the work introduces a new molecular descriptor (ND) that reflects both 2D and 3D topological characteristics of the molecule. Between the retention constant, RM0 and the descriptor ND there is a good correlation, and both RM0, and ND describe sufficiently well the structural (conformational) changes that arise in the process of oxidation of the OH group of the steroid skeleton to an oxo group. On the other hand, the in silico descriptors of lipophilicity, logP (atomic-based prediction) and ClogP (fragment-based prediction) predict the hydrophobicity of bile acid oxo derivatives with a certain error