L. Saunders

ULTRASONIC IRRADIATION OF SOME PHOSPHOLIPID SOLS

Ultrasonic irradiation of turbid sols of egg lecithin and of highly unsaturated synthetic lecithins, breaks down the large particles in the sols into micelles of micellar weight of about 5 × 106. The irradiated sols are clear and do not show any great increase of turbidity over a period of several days; they are capable of solubilising large quantities of cholesterol. The size and shape of micelles in the irradiated sols has been studied by means of viscosity and diffusion measurements and by determination of sedimentation coefficients in the ultra‐centrifuge.

Molecular aggregation in aqueous dispersions of phosphatidyl and lysophosphatidyl cholines

Summary 1. The nature of the molecular aggregates formed in aqueous lecithin, lysolecithin and mixed dispersions are discussed. 2. The experimental results with these dispersions can be explained in terms of three forms of micelles, spherical, helical and folded laminar. 3. Results obtained with synthetic isomeric lecithins are interpreted in terms of the three micellar types; the main factor governing the type formed appears to be the solid angle into which the molecule can be fitted. 4. The effect of ultrasonic irradiation of lecithin sols is considered to be an expulsion of solvent from the aggregates and a rearrangement into folded laminae.

A LIGHT-SCATTERING STUDY OF ULTRASONICALLY IRRADIATED LECITHIN SOLS.

Abstract 1. 1. Light-scattering methods have been used to investigate the change in size and shape of lecithin aggregates in aqueous dispersions undergoing ultrasonic irradiation. 2. 2. It has been shown that large, highly asymmetric particles within the coarse lecithin dispersion are broken down during the irradiation process to produce almost symmetrical aggregates with a particle weight of about 2 ·; 10 6 . 3. 3. Sols irradiated for times greater than 10 min have been shown to be stable over a period of a week.

Sustained release of drugs from ion exchange resins.

THE development of preparations to give sustained release of drugs in the body when administered by mouth, has been recently reviewed’. Most of these preparations are based on physical methods for retarding the release of drug as, for example, by making tablets which disintegrate slowly or by coating pellets with slowly soluble films213. A more continuous and uniform release over a long period is likely to result if the drug is chemically bound to a solid carrier, from which it is slowly released by the action of the digestive fluids. The slowness of the uptake and release of alkaloids from ion exchange resins has been noted by Saunders and Sr i i ra~tava~>~ and it was thought that these resins might provide suitable chemical carriers for drugs in sustained release preparations. Ion exchange resins are extremely insoluble in aqueous liquids and have no toxic effects unless they are given in large enough quantities to disturb the calcium content of the body fluids. When they are administered by mouth, they are likely to spend about two hours in the stomach in contact with an acid fluid of concentration of about 0-1N hydrochloric acid. They will then be moved to the intestine where they will be in contact with a fluid of approximately neutral pH and ionic strength of about that of 0.1N sodium chloride, for several hours. An outline of the properties and structures of ion exchange resins has been given in a review by Saunderse. The common cation exchangers contain either carboxyl or sulphonic acid groups distributed throughout the resin particles. Both types in the hydrogen form (the “form” of a resin is named after the exchangeable ion contained in it) absorb alkaloids from solution, forming resin salts, in which the alkaloid is chemically combined with the exchanger anion. RSO,-H+ + Alk = RS0,-AlkH+

The solubilization of some steroids by phosphatidyl choline and lysophosphatidyl choline

Abstract 1. 1. Quantitative estimations of the amounts of some steroids solubilized by ultrasonic dispersion with phosphatidyl choline in water, have indicated that mono-polar steroids are solubilized to a greater extent than multipolar steroids. Also, of the monopolar steroids studied, those possessing a 5-en structure, were solubilized to a lesser extent than the 4-en-3-one steroids and those with a saturated nucleus. 2. 2. The effect of chain length of the acid present in a series of cholesterol esters on the quantity solubilized by phosphatidyl choline was examined. It was found that as the series was ascended so the quantity solubilized decreased, although the trend was reversed for higher members of the series. 3. 3. Dispersion with lysophosphatidyl choline in the presence of phosphatidyl choline resulted in an increase in the quantity of progesterone solubilized in ultrasonically irradiated aqueous sols.

A LIGHT-SCATTERING STUDY OF LYSOLECITHIN SOLS

Sols of four samples of lysolecithin have been studied by means of a light‐scattering apparatus. The results of a large number of measurements have been analysed statistically. They indicate that the mean molecular weight of the micelles in the sols is 92,400, the experimental error in this estimate being 7 per cent.

The dispersion of cerebral lipids in aqueous media by ultrasonic irradiation

Abstract 1. 1. Optcally-clear sols of ox-brain cerebral lipids prepared by ultrasonic irradiation (16–24 kcycles/sec) have been examined by physicochemical methods. 2. 2. The myelinic figures in the lecithin sols were broken down to disc-shaped micelles with a micellar weight of about 2·106. 3. 3. Sedimentation of dispersions of phosphatidylethanolamine and -serine and sphingomyelin indicated micellar weights similar to that for lecithin. 4. 4. The phospholipid sols, with the exception of phosphatidylethanolamine, were stable over several days and were not flocculated by dilute salt solutions. 5. 5. Sulphatides, unlike cerebrosides, were readily dispersed, due to the acidic groups on the molecules. 6. 6. No evidence for chemical changes resulting from ultrasonic irradiation was obtained from preliminary analyses.

THE PHYSICAL PROPERTIES OF LYSOLECITHIN AND ITS SOLS: Part I.—Solubilities, Surface and Interfacial Tensions

The solubilities of lysolecithin in water and some organic solvents have been determined and the effect of lysolecithin at air‐water and chloroform‐water interfaces examined. The results indicate that lysolecithin has marked surface‐active properties and that a critical micelle concentration occurs in the aqueous sols in the range 1 to 2 times 10−3 per cent weight/volume. The effects of acid, alkali and mono‐ and di‐valent cations on the lowering of the interfacial tensions was found to be small. Lysolecithin had little or no lowering effect on the surface tensions of ethanol and chloroform.

THE PHYSICAL PROPERTIES OF LYSOLECITHIN AND ITS SOLS: Part II. Refractive Indices and Densities of Sols. Micelle Formation

The refractive index difference (nsol‐ nwater) and density difference (ρsol ‐ ρwater) of lysolecithin sols indicate a change in the properties of the sols in the region of 0ṁ02 per cent w/v, above this concentration the refractive index difference:concentration relation and the density difference:concentration relation are linear. Values for the partial specific volumes of lysolecithin in water, calculated from density measurements, are given. Surface tension:concentration measurements at four different temperatures indicate that the critical micelle concentration increases with an increase in temperature. Values for the change in heat content in the molecular aggregation process, calculated from the temperature coefficient of the critical micelle concentration are small and negative, increasing numerically from 3432 calories at 20° to 6100 calories at 40°. The associated entropy changes in this process are small and show a slight increase negatively with an increase in temperature.

Lecithin-cholesterol sols.

Habituation and extinction, and possibly sleep, belong to the same category of phenomena, those of “internal inhibition.” This is a process opposed by reinforcement, for it tends not to appear in its presence (Pavlov, 1960). This might explain the fact that in our rats a conditioned response was unaffected by pyrogallol during the reinforcement stage, whereas pyrogallol clearly enhanced internal inhibitory processes in situations where reinforcement was absent, like habituation, or extinction. The decreased rate of establishment of a conditioned reflex, in view of the results on habituation, may be due to the fact that the ‘‘inhibitory property” of the conditioned stimulus (Konorski, 1948) was increased by pyrogallol. In no experiment did our rats show any motor disturbance nor any apparent neurological symptom. The response to shock itself was obviously unmodified by pyrogallol. Our data on enhanced internal inhibition by pyrogallol, if in fact due to the increase in cerebral catecholamines, may be in agreement with those that ascribe a “central inhibitory,” sleep-inducing property to centrally active catecholamines (Bass, 1914; Domer and Feldberg, 1960). Attention is obviously drawn towards those diencephalic and mesencephalic structures which are normally rich in these transmitters (Vogt, 1954).