Formation Of Micellar Complex Research Articles

Effects and mechanism of epimedium polysaccharide on solubility of icariin and baohuoside Ⅰ

This study evaluated the effects of epimedium polysaccharide(EPS) on the solubility of icariin and baohuoside Ⅰ so as to preliminary explore its solubilization function and the underlying mechanism. The solubility of these two insoluble flavonoids in water and polysaccharide solutions was compared by high performance liquid chromatography, and the mechanism was investigated by diffe-rential scanning calorimetry(DSC) and critical micelle concentration determination. The results indicated that their solubilization in crude EPS solutions was concentration-dependent. The solubility of icariin and baohuoside Ⅰ in 20 mg·mL~(-1) EPS-1-1 was 9.05 times and 5.76 times that in water, respectively; while their solubility in 20 mg·mL~(-1) EPS-2-1 was 10.55 and 8.39 times that in water, respectively. The change of the DSC thermograms suggested the formation of new complexes from icariin and baohuoside Ⅰ with polysaccharides. The critical micelle concentrations proved the micellar properties of both EPS-1-1 and EPS-2-1. In short, EPS can significantly increase the solubility of icariin and baohuoside Ⅰ, the mechanism of which may be related to the formation of micellar complexes between EPS and insoluble flavonoids.

Lipid-lowering effects of Coffea arabica pulp aqueous extract in Caco-2 cells and hypercholesterolemic rats

BackgroundCoffea arabica pulp (CP) is the first by-product obtained from coffee berries during coffee processing. The major constituents of CP, including chlorogenic acid, caffeine, and epicatechin exhibit anti-hyperlipidemic effects in in vitro and in vivo models. Whether Coffea arabica pulp aqueous extract (CPE) has a lipid-lowering effect remains unknown. PurposeThis study examined the effect of CPE on cholesterol absorption, and identified the mechanisms involved in lowered cholesterol in in vitro and in vivo models. MethodsUptake of [3H]-cholesterol micelles and the mode of CPE inhibition were determined using human intestinal Caco-2 cells, and subsequently, confirmed using isolated rat jejunal loops. In addition, the 12-week high-fat diet-induced hypercholesterolemic rats (HF) received either CPE (1000 mg/kg BW), a sole and high dose which was selected because it contained approximately 12 mg of CGA that was previously shown to have lipid-lowering effects, or ezetimibe (10 mg/kg BW), a cholesterol inhibitor. The rats were divided into HF, HF ++ CPE, and HF ++ ezetimibe groups for the next 12 weeks. Normal rats received a normal diet (ND) and CPE (ND + CPE). Body weights and lipid profiles were evaluated. Cholesterol transporter, Niemann–Pick C1-Like 1 (NPC1L1), protein expression and liver X receptor alpha (LXRα) mRNA expression were determined. In vitro micellar complex properties were also investigated. ResultsCPE inhibited [3H]-cholesterol micelle transport in Caco-2 cells and rat jejunal loops in a dose-dependent, non-competitive manner partly by decreasing membrane NPC1L1 expression. Congruently, CPE and its major constituents activated LXRα which, in turn, down-regulated NPC1L1. Furthermore, CPE interfered with physicochemical characteristics of cholesterol mixed micelles. These data were consistent with decreased body weight and slowed body weight gain and improved lipid profiles by CPE in hypercholesterolemic rats while no change occurred in these parameters in normal rats. Down-regulated intestinal NPC1L1 expression mediated by increased LXRα mRNA were also observed in HF ++ CPE and ND + CPE rats. ConclusionCPE has a cholesterol-lowering effect in in vitro and in vivo via inhibition of intestinal cholesterol absorption by down-regulating NPC1L1 mediated LXRα activation and interfering with micellar complex formation. Accordingly, CPE could be developed as nutraceutical product to prevent dyslipidemia-induced obesity and insulin resistance.

Hydrogen-Bonding-Induced Complexation of Polydimethylsiloxane-graft-poly(ethylene oxide) and Poly(acrylic acid)-block-polyacrylonitrile Micelles in Water

Polydimethylsiloxane-graft-poly(ethylene oxide) (PDMS-g-PEO) copolymers form micelles in water with PDMS as the core and PEO as the corona. The introduction of poly(acrylic acid)-block-polyacrylonitrile (PAA-b-PAN) block copolymers in water leads to the formation of micellar complexes due to the hydrogen bonding between carboxyl groups and ether oxygens among the PAA and PEO chains in the corona of the micelles. The effects of pH, molar ratios (r) of PAA/PEO, and the standing time on the directly mixing these two micelles in water have been investigated using laser light scattering (LLS) and transmission electron microscopy (TEM). Our results showed that the complexation between PAA and PEO in the corona was greatly enhanced at a pH below 3.5. For a fixed pH value, the interactions between these two micelles in water were governed by the value of r. At r < ∼0.6, mixing the two micelles in water resulted in a large floccule because the smaller PAA-b-PAN micelles act as physical cross-links, which are absorbed onto one PDMS-g-PEO micelle and simultaneously bonded to PEO chains on the other micelles, forming bridges and causing flocculation. At ∼0.6 < r < ∼1.2, the mixing led to stable micellar complexes with a layer of PAA-b-PAN micelles absorbed onto the initial PDMS-g-PEO micelles. At r > ∼1.2, the resultant micellar complexes first remained stable, but they precipitated from solution after a long time standing.

New findings on melatonin absorption and alterations by pharmaceutical excipients using the Ussing chamber technique with mounted rat gastrointestinal segments

We examined how melatonin absorption was affected by pharmaceutical excipients using the Ussing chamber technique with mounted rat gastrointestinal (GI) segments. Melatonin absorption occurs throughout the GI tract, with the greatest absorption being in the rectum and ileum and the least in the stomach. Melatonin can be classified as a low permeability drug. P-glycoprotein (P-gp) does not affect melatonin absorption but transported rhodamine 123, a well-known P-gp substrate. The possibility of saturating P-gp by melatonin was excluded. Sodium cholate (0.5%) increased melatonin absorption, but decreased absorption at higher concentrations (1.0% and 5.0%). Sodium oleate (0.5% and 1.0%) consistently decreased melatonin absorption. Pharmaceutical excipients increased the absorption of Lucifer yellow (100 μg/mL), a paracellular probe but decreased the absorption of melatonin above the critical micelle concentration (cmc), suggesting that melatonin was transported mainly by transcellular pathway. Sodium cholate and sodium oleate, when above the cmc, resulted in micellar complexes as revealed by 1H NMR spectra and particle size distribution. Histology tests showed mucosal damage of jejunum tissues in the presence of these excipients. The balance of tissue damage by the formation of micellar complexes could affect the melatonin absorption. This information on melatonin absorption behaviors and its modulation by pharmaceutical excipients can be used in further oral dosage formulations to affect circadian rhythm.

Molecular Dynamics Simulation for the Effect of Chain Length of Spacer and Tail of Cationic Gemini Surfactant on the Complex with Anionic Polyelectrolyte

Abstract Interaction of anionic polyelectrolyte with cationic gemini surfactant has been investigated by coarse-grained molecular dynamics simulation. Polyelectrolyte facilitates the oppositely charged ionic surfactants to aggregate by suppressing the electrostatic repulsion between ionic head groups leading to the formation of micellar complex. With addition of surfactant, the conformation of polyion chain changes from stretched to random coiled to spherical, and at the same time more free micelles are formed by surfactants in mixtures. Increasing the length of spacer or tail chain in gemini surfactant will weaken its interaction with polyelectrolyte and simultaneously strengthen its tendency to self-assemble. The simulation results are consistent with experimental observations and reveal that the electrostatic interaction plays an important role in the interaction of polyelectrolyte with gemini surfactant.

Molecular dynamics simulation of polyelectrolyte with oppositely charged monomeric and dimeric surfactants

Interactions of anionic polyelectrolyte (PE) with cationic monomeric (MS) and dimeric surfactants (DS) have been investigated by coarse-grained molecular dynamics (MD) simulation. A PE/surfactant mixture is observed to evolve over time into micellar complex of increasing size. The critical aggregation concentration (CAC) is qualitatively found to be much lower than the critical micellization concentration (CMC) of the free surfactant. Compared to the monomeric analog, a DS interacts more strongly with the oppositely charged polyion chain. The equilibrium complex size becomes larger with increasing surfactant concentration. Simulation results are consistent with experimental observations and reveal that the electrostatic and hydrophobic interactions play an important role in the formation of micellar complex.

Molecular assembly and subcellular distribution of ATP-sensitive potassium channel proteins in rat hearts

Cardiac ATP-sensitive K + (K ATP) channels are proposed to contribute to cardio-protection and ischemic preconditioning. Although mRNAs for all subunits of K ATP channels (Kir6.0 and sulfonylurea receptors SURs) were detected in hearts, subcellular localization of their proteins and the subunit combination are not well elucidated. We address these questions in rat hearts, using anti-peptide antibodies raised against each subunit. By immunoblot analysis, all of the subunits were detected in microsomal fractions including sarcolemmal membranes, while they were not detected in mitochondrial fractions at all. Immunoprecipitation and sucrose gradient sedimentation of the digitonin-solubilized microsomes indicated that Kir6.2 exclusively assembled with SUR2A. The molecular mass of the Kir6.2–SUR2A complex estimated by sucrose sedimentation was 1150 kDa, significantly larger than the calculated value for (Kir6.2) 4–(SUR2A) 4, suggesting a potential formation of micellar complex with digitonin but no indication of hybrid channel formation under the conditions. These findings provide additional information on the structural and functional relationships of cardiac K ATP channel proteins involving subcellular localization and roles for cardioprotection and ischemic preconditioning.

Interaction of Human Apolipoprotein A-I with Dipalmitoylphosphatidylcholine in Vesicular and Micellar Complexes

The interactions of human apolipoprotein A-I (apo A-I) with dipalmitoylphosphatidylcholine (DPPC) in vesicular complexes at low protein concentrations and in micellar complexes at high protein concentrations are compared. The C-terminal segment of this protein, with a relative molecular weight (Mr) of about 11,000, is protected on trypsin treatment of apo A-I-vesicle complexes. A segment within the sequence from Leu-189 to Arg-215 of apo A-I penetrates the hydrophobic interior of the membrane, as found in a hydrophobic labeling experiment involving 3-(trifluoromethyl)-3-(m-[125I]iodophenyl)-diazirine ([125I]TID). No appreciable stretch of apo A-I in micellar complexes was found to be protected from the tryptic digestion. This indicates that the interactions of apo A-I with lipids in the vesicular and micellar complexes are different. The binding equilibrium of apo A-I as to DPPC vesicles at low protein concentrations, as studied by hydrophobic labeling of the bilayer-penetrating segment, is reached within about 1 h, while the formation of micellar complexes at high protein concentrations takes about 24 h at 42 degrees C. Time-dependent labeling studies involving photoreactive phosphatidylcholine (PC) with high apo A-I concentrations suggested an initial interaction with the head group region of the bilayer followed by interaction with the tail ends of the acyl chains of the lipid. A possible mechanism for the micellization process is discussed.

Apomyoglobin forms a micellar complex with phospholipid at low pH

Apomyoglobin was found to break down phosphatidylcholine vesicles to form a micellar complex at pH 4. Size reduction during this process was observed by measuring light scattering at 400 nm and by passing the complex through a gel-filtration column. Micellar complex formation was confirmed by electron microscopy.

Intestinal absorption of a .BETA.-adrenergic blocking agent nadolol. III Nuclear magnetic resonance spectroscopic study on nadolol-sodium cholate micellar complex and intestinal absorption of nadolol derivatives in rats.

The stable micellar complex formation between nadolol and sodium cholate was studied. The proton nuclear magnetic resonance spectroscopic study showed that the signals of protons in the hydrophobic site of cholic acid, i.e., the methine signals of C-7 and C-12, and the methyl signals of C-18 and C-19. exhibited rather larger shifts than those of the other protons. The longitudinal relaxation times of the aromatic ring protons (C-4, C-6, C-7 and C-8) of nadolol were shortened by about 10% in the presence of sodium cholate, indicating that the aromatic ring protons were more immobilized upon complex formation. These results suggest that the hydrophobic protons of sodium cholate and nadolol interact with each other, and complex formation with the hydrophobic protons inside and the hydrohilic protons outside may occur in aqueous solution. The intestinal absorption of four nadolol derivatives was examined by the in situ ligated loop method in rat jejunum in the presence of sodium cholate. The absorption of the trans-2, 3-diol isomer was inhibited as effectively as that of nadolol. The absorption of the 2-and 3-monohydroxy derivatives and cis-2, 3-dimethoxy derivative was inhibited by sodium cholate at 1 h after dosing, but no inhibition was observed at 4 h. This absorption behavior of nadolol derivatives was well correlated with the apparent dissociation constants of their micellar complexes with sodium cholate. It is concluded that the stability of the complexes of β-adrenergic blocking agents with sodium cholate depends upon the steric features of both hydrophobic and hydrophilic parts of the drug molecules. The hydrophilic cis-2, 3-diol moiety of nadolol plays an important role in stabilizing the micellar complex with sodium cholate.

Kinetics of phospholipid transfer between liposomes (neutral or negatively charged) and high-density lipoproteins: a spin-label study of early events

The kinetics of spin-labeled phosphatidylcholine transfer between vesicles and HDL particles exhibited a two-phase process, as seen by ESR spectroscopy. The results were analyzed by considering several possible steps in the overall transfer, whose aspects were also studied: (i) micellar complex formation after HDL apolipoprotein-vesicle mixture, (ii) the rate of PC transfer from the micellar complex to HDL, (iii) the rate of the reverse reaction between overloaded HDL particles and other particles such as HDLs, LDLs, and lipid vesicles. The results agree most convincingly with a mechanism in which the diffusion of phospholipids into the HDL-endogenous lipids is the limiting step, occurring as a two-step process. In addition, we observed a negative charge effect on the lipid transfer rates and yields.

Effect of synthetic surfactants on drug absorption in the presence of a physiologic surfactant, sodium taurocholate, in rats.

The effect of synthetic surfactants and their binary mixture with a physiologic one, sodium taurocholate (STC), on the intestinal absorption of drugs was examined in rats by using the in situ recirculation technique. Synthetic surfactants investigated in this study were nonionic polysorbate 80 (PS-80), cationic cetyltrimethylammonium bromide (CTAB), and anionic sodium lauryl sulfate (SLS). The surfactant action on the mucosal membrane seemed to be the same magnitude as the stronger one of the two components, except in the case of CTAB, as estimated by the enhancement effect on sulfaguanidine absorption. The action of CTAB was increased in the presence of STC. The action of surfactants in the aqueous solution, an intraluminal action, was examined by using quinine as a model drug. The micellar interaction of the drug with an ionic surfactant, CTAB or SLS, was reduced by the addition of STC, whereas, that with a nonionic surfactant, PS-80, was increased as estimated by a dynamic dialysis technique. The inhibitory effect on quinine absorption was approximately proportional to the degree of the micellar complex formation. Two other model drugs, imipramine and sulfadimethoxine, were further examined and the possible mechanisms of these effects were discussed.

Kinetics and mechanism of apolipoprotein A-I interaction with L-alpha-dimyristoylphosphatidylcholine vesicles.

The dynamics of human apolipoprotein A-I (apo A-I) interaction with dimyristoylphosphatidylcholine (DMPC) vesicles were investigated in a 4000:1 DMPC/apo A-I (mol/mol) mixture where all the protein is bound to DMPC in stable vesicular complexes, and in a 100:1 DMPC/apo A-I (mol/mol) mixture which gives micellar complexes at equilibrium. Gel filtration and fluorescence methods (polarization and intensity) were used to follow the reaction kinetics. The binding of apo A-I to DMPC vesicles is a very rapid process which takes only a few minutes, while the formation of micellar complexes takes several hours at 25 degrees C and involves saturated complexes of apo A-I . DMPC and free apo A-I. The rate-limiting step in micellar complex formation is the breakdown of saturated vesicle . apo A-I complexes, a process that exhibits first order kinetics with a rate constant k = 0.22 h-1 and a half-life t 1/2 = 3 h 9 min.

Effect of cholesterol on the formation of micellar complexes between bovine A-I apolipoprotein and L-alpha-dimyristoylphosphatidylcholine

Effect of cholesterol on the formation of micellar complexes between bovine A-I apolipoprotein and L-alpha-dimyristoylphosphatidylcholine

Intestinal absorption of drugs from solubilized systems of long-chain fatty acids in the rat.

The effects of long-chain fatty acids solubilized by sodium taurocholate on the absorption of various water-soluble drugs from the rat small intestine were investigated using the in situ perfusion technique. The addition of 20 mM sodium taurocholate alone or together with lower concentration of oleic acid increased the absorption of poorly absorbable procaine amide, while with higher concentration of oleic acid decreased the absorption of the drug. The addition of oleic acid and monolein significantly increased the formation of micellar complex of well absorbable 2-allyloxy-4-chloro-N-(2-diethylaminoethyl) benzamide hydrochloride (A. C. D. B.) and inhibited the absorption of it, compared to those produced by 20 mM sodium taurocholate alone. The results suggested that the effects of long-chain fatty acids on the intestinal absorption of drugs in the presence of sodium taurocholate were mediated via two mechanisms : modification of the permeability of the membrane and micellar complexation of the drug.

Structure of the myelin sheath as a function of concentration of ions.

Abstract Homogenization of cerebral white matter or of peripheral nerve with 1 M NaCl caused the formation of micellar complexes bounded on the outside by a hydrophilic layer (“oil-in-water”). Homogenization of such tissues in 0.5 M CaCl 2 caused the formation of lipophilic complexes. Histochemical experiments yielded comparable results. The implications of these observations for the study of the structure of myelin are discussed. Formation of oil-in-water and water-in-oil systems were associated respectively with the formation of aqueous channels or of oily pillars across the lamellae of myelin or across cell membrane layers. The possible formation of such channels in vivo as a result of localized changes in lipophilic-hydrophilic ratio may be used to explain a number of biological phenomena.