Kellaway Iw

Direct effect of bile salts and phospholipids on the physical properties of mucus.

Reflux of duodenal contents into the stomach has been implicated in the disruption of mucosal defence and the subsequent occurrence of gastric ulcer. The change produced in the rheological properties following the addition of bile salts and phospholipids to mucus samples was used to assess resultant structural changes. Sodium deoxycholate, sodium taurodeoxycholate, sodium glycocholate, and lysophosphatidylcholine decreased both viscosity and elasticity, indicating that structural breakdown had occurred, whereas phosphatidylcholine could not be shown to have any effect. It is therefore suggested that some of the ulcerogenic activity of naturally occurring surfactants may be associated with their ability directly to reduce mucus consistency.

Thermodynamics of partitioning and efflux of phenothiazines from liposomes

SummaryThe partitioning of nine phenothiazines between dimyristoylphosphatidylcholine (DMPC) liposomes and 0.9% wt/vol saline at pH 6 has been studied both below and above the phase transition temperature (Tc) of the phospholipid. Higher partitioning was observed aboveTc. Both the entropy and enthalpy of partitioning were positive below and aboveTc, and a linear relationship between the entropy and enthalpy has been derived. In general, the partitioning and transport of alkylaminophenothiazines in DMPC liposomes over the temperature range of 5 to 40°C is entropically controlled. The entropies and enthalpies of partitioning of various groups in the phenothiazine structure have been calculated.No relationship was found between particle size of the DMPC liposomes and the equilibrium partition coefficient at 25°C. However, the particle size of liposomes did increase with increasing acyl chain length of the phospholipid.Using differential scanning calorimetry, the enthalpy and entropy of transition of the DMPC liposomes in the absence and presence of phenothiazines has been calculated. The temperature dependence of the first-order rate constant of trimeprazine tartrate transport in DMPC liposomes was investigated and was found to be maximum at theTc of the phospholipid.

The solubilization of progesterone by mixed bile, salt-phospholipid sols

The solubility of progesterone was determined in several different bile salt-phospholipid mixtures, and it is concluded that: (1) The solubility in unconjugated bile salts is greater than in the conjugated analogues, and the solubility in deoxycholate solutions is twice that in cholate solutions. (2) Substitution of hydroxyl groups in the 11 and 21 positions of progesterone increases solubility, whilst substitution in the 17-position decreases solubility in bile salt solutions. (3) Progesterone solubility in mixed bile salt solutions is proportional to the mole ratio of the surfactant mixture. (4) Sodium deoxycholate (SDC)-phospholipid sols show no such linear solubilizing properties; a minimum occurring at a mole ratio of SDC to phospholipid of 1 : 4. (5) There is a break in the solubility curve of progesterone in lysophosphatidycholine (LPC)/phosphatidylcholine (PC) mixtures at a mole ratio of 65 : 35 coincident with maximum viscosity. (6) Introduction of SDC into LPC/PC mixtures results in decreased progesterone solubility.

The effect of ageing on the rheological properties of gelatin gels

The effect of ageing at 4° on the viscoelastic properties of 1·5 and 2·0% acid and alkaline processed gelatin gels has been investigated. Viscoelastic properties were not markedly affected by ageing time although evidence of a decrease in gel structure with increasing ageing time was apparent. This has been tentatively attributed to hydrolysis of amide links. 1·5% alkaline gels were shown to be more rigid than the corresponding acid gels and this has been discussed in terms of differences in molecular weight, polydispersity, charge and charge distribution.

The interaction of penicillins with phospholipids.

The interaction of the antibiotics, penicillin G and ampicillin, with sonicated sols of phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylserine has been examined by Sephadex gel nitration and dynamic dialysis. Nuclear magnetic resonance spectroscopy provided evidence of a predominantly hydrophobic interaction between the antibiotics and the phospholipids, phosphatidylserine and phosphatidylcholine. Confirmation of hydrophobic interaction was provided by a rheological investigation of the effects of urea and guanidine hydrochloride on the antibiotic‐phospholipid complex. Penicillin G was found to interact to a greater degree than ampicillin, a result which is of interest in the light of present knowledge of in vivo activity of these antibiotics.

Rheological studies on mixed phospholipid sols and their interaction with penicillins. I. Continuous shear viscometry.

Abstract The effects of sonication and ageing of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) sols have been examined. Ageing was found to significantly alter the nature of the flow curves obtained for sonicated mixtures; only after 48 hr was reproducibility obtained. Rheological studies on aged mixed sols indicated behaviour similar to that previously reported. Addition of urea and guanidine hydrochloride in concentrations up to 8 M indicated hydrophobic interaction between PC and LPC. Addition of Penicillin G and Ampicillin to mixed PC/LPC sols indicated that Penicillin G interacted to a greater degree than Ampicillin; pronounced Penicillin G interaction was observed in a mixed sol containing 60% PC, 40% LPC, a system where the asymmetry of the aggregates is at a minimum. Ampicillin appeared to interact to a greater degree with mixtures containing more LPC than PC. Differences in hydrophobic interaction were indicated by use of urea and guanidine hydrochloride, which is of interest in the light of present knowledge regarding the in vivo activity of these antibiotics.

Phenothiazine transport across liquid-lipid, phospholipid and soft polymer membranes

Abstract The transport of phenothiazines across phospholipids, isopropyl myristate (IPM) and polydimethylsiloxane (PDMS) membranes has been investigated using the rotating diffusion cell. The aqueous diffusion coefficients and the diffusivities across the PDMS membranes have been determined for the same phenothiazines. With phospholipids, the transport rate constants for mequitazine decreased in the following order: phospholipid free interface > DSPC > DPPC > DMPC. On comparing the transport rate constants across egg phosphatidylcholine liposomes, IPM and PDMS, no simple correlation was found between any two of the three model membranes. The structure of the membrane phase thus appears to be critical in determining the transport characteristics of complex molecules.

The effect of blending on the rheological properties of gelatin solutions and gels

The effect of blending on rheological properties for an acid and alkaline processed gelatin has been investigated. Blending of weak gels (1·0–3·5% w/v at 25°), resulted in a decrease in gel rigidity whereas in the stronger gels (5–50% w/v at 25°) and solutions (18% and 30% w/v at 35°), an increase occurred. The decrease in structure in the weak gels is considered to be due to coulombic effects, minimum strength occurring for a mixture which possessed zero charge in solution. A tentative explanation for effects in rigid gels and concentrated solutions is offered.

The interaction of penicillins with mixed phospholipid sols. II. Creep viscometry

Abstract Addition of the antibiotics, Penicillin G and Ampicillin, to mixed phosphatidylcholine (PC)-lysophosphatidylcholine (LPC) dispersions indicated that Penicillin G interacted to a greater degree than Ampicillin, confirming continuous shear viscometry studies. The product of interaction appeared to depend on whether sols or gels were investigated. The majority of systems studied could be represented by an eight-parameter Kelvin-Voigt model, and were found to exhibit varying degrees of viscoelasticity. The biological significance of the results is discussed.

The effect of bile salts on the interfacial transport of phenothiazines

Abstract The transport of phenothiazine drugs across isopropyl myristate (IPM) membranes has been studied using the rotating diffusion cell. Interfacial transport rate constants across aqueous—IPM and IPM—aqueous interfaces have been calculated for mequitazine and perphenazine. Although the interfacial barriers were not ratelimiting, they were significant. The rate-limiting barrier to the mequitazine and perphenazine transport was found to be the diffusion across IPM. The effect of bile salts on the transport of mequitazine across IPM was investigated. The hypothesis that ion-pairing may increase the transport of drugs is not supported by this study.