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At least 19 recordsLinked to original sources

The effect of oil components on the physicochemical properties and drug delivery of emulsions: tocol emulsion versus lipid emulsion.

An emulsion system composed of vitamin E, coconut oil, soybean phosphatidylcholine, non-ionic surfactants, and polyethylene glycol (PEG) derivatives (referred to as the tocol emulsion) was characterized in terms of its physicochemical properties, drug release, in vivo efficacy, toxicity, and stability. Systems without vitamin E (referred to as the lipid emulsion) and without any oils (referred to as the aqueous micelle system) were prepared for comparison. A lipophilic antioxidant, resveratrol, was used as the model drug for emulsion loading. The incorporation of Brij 35 and PEG derivatives reduced the vesicle diameter to <100nm. The inclusion of resveratrol into the emulsions and aqueous micelles retarded the drug release. The in vitro release rate showed a decrease in the order of aqueous micelle system>tocol emulsion>lipid emulsion. Treatment of resveratrol dramatically reduced the intimal hyperplasia of the injured vascular wall in rats. There was no significant difference in this reduction when resveratrol was delivered by either emulsion or the aqueous micelle system. The percentages of erythrocyte hemolysis by the emulsions and aqueous micelle system were approximately 0 and approximately 10%, respectively. Vitamin E prevented the aggregation of emulsion vesicles. The mean vesicle size of the tocol emulsion remained unchanged during 30 days at 37 degrees C. The lipid emulsion and aqueous micelle system, respectively, showed 11- and 16-fold increases in vesicle size after 30 days of storage.

Animals↗

Lipid emulsions of palmitoylrhizoxin: effects of particle size on blood dispositions of emulsion lipid and incorporated compound in rats.

Emulsion formulations of various particle sizes for the highly lipophilic antitumour agent, RS-1541 (13-O-palmitoylrhizoxin), were prepared using dioctanoyldecanoylglycerol (ODO) as lipids and polyoxyethylene-(60)-hydrogenated castor oil (HCO-60) as a surfactant. These emulsions were evaluated as injectable drug carriers and compared with a colloidal solution. Both in vitro and in vivo after i.v. administration, RS-1541 was distributed into lipoproteins from the colloidal solution. When applied as emulsions of various particle sizes (124-419 nm) in vitro, RS-1541 was retained and stabilized within the emulsions. In the in vivo study, however, retention of RS-1541 in the emulsions after i.v. injection depended on their size. The small-particle emulsions (94-112 nm) resulted in long retention, and the large-particle emulsions (415-474 nm) led to short retention. Lipolysis rates of emulsion particles by lipoprotein lipase also depended on their size, indicating rapid lipolysis for small-particle emulsions (133 nm). However, the lipolysis was not such an extensive one, showing 10-30% release of capric acid from ODO within 6 h. Blood dispositions of capric acids approximately paralleled those of RS-1541 after i.v. injection of various particle size emulsions (130-368 nm) to rats, although relatively rapid eliminations of capric acids compared with RS-1541 were observed for the small-particle size emulsions (130 nm). These results suggest that when injected as emulsion formulations, the highly lipophilic antitumour agent, RS-1541, has behaviour similar to that of the emulsion particles in the body, which is dependent on the size of the latter. Thus, by properly selecting the particle size, lipid emulsions consisting of ODO and HCO-60 are expected to be effective and useful DDS carriers for RS-1541.

Animals↗

Influence of the emulsion components and preparation method on the laboratory-scale preparation of o/w emulsions containing different types of dispersed phases and/or emulsifiers.

Emulsification is a complex process, strongly influenced by emulsion composition as well as by preparation procedure, and the characterisation of emulsions with regard to their structure and stability can be carried out with many different methods. To evaluate the influences of emulsion composition and preparation procedure on the structure and properties, oil-in-water emulsions were prepared using the model dispersed phase dodecane and the surfactant Tween on the one hand and the real food components sunflower oil (dispersed phase) and casein (emulsifier) on the other hand. The emulsions were prepared in a small laboratory-scale with a turbo-mixer alone and in combination with ultrasonic treatment. The emulsion activity was measured by photometry, the emulsion stability was evaluated visually and the droplet size was determined by laser particle analysis. The results of the investigations made with the model substances agree only partly with those made with the real food substances. For the model emulsions strong correlation were found between the emulsion activity and the particle sizer data because of the high purity and the defined structure of the model substances. On the contrary, for the emulsions made with the real food components sunflower oil and sodium caseinate the correlation were much weaker. Therefore a proper characterisation of the structure and properties of food emulsions requires examinations with several methods which are independent from each other. Furthermore, for laboratory-scale emulsification the combination of turbo-mixer and ultrasonic treatment is suitable to obtain small droplets and a narrow droplet distribution also for very small emulsion volumes.

Emulsions↗

In vitro release, pharmacokinetic and tissue distribution studies of doxorubicin hydrochloride (Adriamycin HCl) encapsulated in lipiodolized w/o emulsions and w/o/w multiple emulsions.

The lipiodolized w/o emulsion or w/o/w multiple emulsion containing Doxorubicin hydrochloride (1; Adriamycin HCl) with different emulsifiers was prepared to evaluate in vitro sustained-release behavior, pharmacokinetic and tissue distribution function in Sprague Dawley (SD) rats. The results of dissolution indicate that the release of 1 was significantly sustained for both emulsions when HCO-60 (polyoxyethylene (60) hydrogenated castor oil) was used as an emulsifier. The serum concentration of 1 was reduced and prolonged for both emulsions with the increase of HCO-60. The C(max) level was lowered and T(max) value was delayed after administration of w/o emulsions with higher HCO-60 concentration. The apparent terminal half-life for 1 released from some emulsions with higher concentration of HCO-60 was 3-folds higher than that of the 1 solution. The clearance of some w/o or w/o/w ADR emulsions also decreased with the increase of HCO-60. Not only the concentration of 1 in heart and kidney decreased significantly after the administration of w/o emulsions with the higher concentration of HCO-60, but also the hepatic concentration of 1 was higher and increased with HCO-60 concentration. The hepatic 1 level became lower after administration of w/o/w multiple emulsions with the increase of HCO-60; however, the concentration of 1 in heart, lung and spleen increased somewhat. The results indicate that lipiodol and HCO-60 seemed to play an important role in the prolongation and selective retention of w/o emulsion or w/o/w multiple emulsion, in vitro and in vivo.

Animals↗

Liposome-stabilized oil-in-water emulsions as adjuvants: increased emulsion stability promotes induction of cytotoxic T lymphocytes against an HIV envelope antigen.

Protective or therapeutic immunity against HIV infection is currently believed to require both antibody and CTL responses against the envelope protein. In the present study, the adjuvant activity of a unique oil-in-water emulsion, in which liposomes containing lipid A (LA) and encapsulated antigen served as the emulsifying agent, was examined in mice using oligomeric gp140 (ogp140) derived from the HIV-1 envelope as the antigen. Emulsions rendered either highly stable or unstable by altering the ratio of liposomes to oil were used to examine the effect of stability of the emulsion on adjuvant activity. Stable and unstable emulsions had similar potencies for inducing both IgG antibodies to ogp140 and antigen-specific T-lymphocyte proliferation. Stable emulsions, but not unstable emulsions, induced antigen-specific CTL responses, possibly because of the depot effect of the stable emulsions. Furthermore, stable emulsions induced lower IgG2a/IgG1 ratios than the unstable emulsions. We conclude that stable liposomal oil-in-water emulsions provide an effective means of obtaining both antibody and CTL responses against an HIV envelope antigen.

AIDS Vaccines↗

Interaction between erythrocytes and free phospholipids as an emulsifying agent in fat emulsions or drug carrier emulsions for intravenous injections.

Hemolysis caused by the interaction between rabbit erythrocytes and oil-in-water emulsions (e.g., fat emulsions or drug carrier emulsions for intravenous injections) prepared with various oil concentrations was investigated. In emulsions prepared with oil concentrations in the range of 2.5-12.5%, the percentage of both hemolysis and free purified egg yolk lecithins (PEL) in the water phase of the emulsions decreased with the increased oil concentration and became constant above 12.5% oil concentration. The change in free PEL percentage in the water phase of the emulsions prepared with various oil concentrations showed the same relationship as that of the percentage hemolysis caused by the interaction between rabbit erythrocytes and emulsions prepared with various oil concentrations. No hemolysis caused by an interaction between rabbit erythrocytes and vesicles prepared with PEL at a concentration of 0.012% was observed. However, hemolysis levels of 64.2% and 91.1% were observed at PEL concentrations of 0.12% and 1.2%, respectively. These results led to the conclusion that hemolysis caused by the interaction between erythrocytes and emulsions was due to PEL vesicles in the water phase of the emulsions.

Animals↗

Preparation of tributyrin emulsion and characterization of the binding of the emulsion particles to low-density lipoprotein in vitro.

Tributyrin has been shown to be an effective antitumor agent alone or in combination with other chemotherapeutic agents in vitro. Because tributyrin exists as an oil, it could be formulated as an emulsion to facilitate its delivery. The aim of this study was to develop a tributyrin emulsion with affinity to low-density lipoprotein (LDL). The tributyrin emulsion was prepared by sonication. Sizes of the different fractions of the emulsion particles separated by ultracentrifugation were determined. Cholesterol was found to decrease the particle size slightly because of its condensing effect. The emulsion monolayer prepared was proved to bind effectively with LDL in vitro. The dissociation constant and binding maximum to LDL of the emulsion fraction 1 with smaller particle sizes were 0.1236 microM and 0.4140 mmol/mol, and that of the fraction 2 with larger particle sizes were 0.0635 microM and 0.2654 mmol/mol, respectively. These results suggested that the binding ability of tributyrin emulsion depended on the component of the monolayer as well as the size of the emulsion particles. The potential pharmaceutical applications of this tributyrin emulsion are discussed.

Cholesterol, LDL↗

Novel affinity separations based on perfluorocarbon emulsions. Development of a perfluorocarbon emulsion reactor for continuous affinity separations and its application in the purification of human serum albumin from blood plasma.

Perfluorocarbon affinity emulsions are generated by the homogenisation of a perfluorocarbon oil with a polymeric fluorosurfactant previously derivatised with an affinity ligand and subsequently cross-linked in situ. This procedure gives rise to a novel liquid affinity adsorbent that can be used for continuous protein purification. Discrete emulsion droplets were found to be unstable when pumped for prolonged periods; however, when flocculated, the emulsion floccules with diameters of around 125 microns, were very stable and sedimented faster. A four-stage reactor unit (perfluorocarbon emulsion reactor for continuous affinity separations, PERCAS) was designed and constructed to carry out continuous separations, and exploited the unusual properties of the absorbent, i.e. liquid nature and high density. Each of the four stages of PERCAS consisted of a mixing tank, for contacting between emulsion phase and aqueous phase, adjacent to a settling tank for the subsequent separation of emulsion from the aqueous phase. Using PERCAS adsorption, washing, elution and re-equilibration of the emulsion could be carried out continuously with emulsion recycle. Using single-component adsorption of human serum albumin to a perfluorocarbon affinity emulsion derivatised with the triazine dye C.I. Reactive Blue 2, PERCAS was optimised with respect to flow-rates and input concentrations. The work was then extended to the continuous purification of essentially homogeneous human serum albumin from blood plasma.

Adsorption↗

Evaluation of milk fat-globule membrane (MFGM) emulsion for oral administration: absorption of alpha-linolenic acid in rats and the effect of emulsion droplet size.

The performance of milk fat-globule membrane (MFGM) emulsion as an oral dosage form was evaluated in rats using [14C]alpha-linolenic acid as a lipophilic model solute. For emulsions prepared by homogenization alone, the area under the plasma concentration versus time curve (AUC) after oral administration tended to be larger for MFGM emulsion, 35.0 +/- 2.5 micrograms eq.h/ml (mean +/- S.E., n = 3), than for Tween 80 emulsion, 28.5 +/- 0.6 micrograms eq.h/ml at p < 0.1, though the peak plasma concentration (Cmax) and the time required to reach Cmax (Tmax) were not significantly different. The absorption in the intestinal loop was not significantly different between the two emulsions, either. Thus, MFGM emulsion, compared with Tween 80 emulsion, did not show an obvious advantage or enhancement in the oral and intestinal absorption of alpha-linolenic acid, except for a slight increase in AUC. However, MFGM could be a good alternative to a synthetic emulsifier for oral use, considering that it is of natural origin and may be safer. In addition, it was shown that the AUC, as well as the absorption in the intestinal loop, was decreased for a MFGM emulsion in which the droplet size was reduced by sonication, presumably because of the observed decrease in alpha-linolenic acid concentration in the water phase, which was assumed to be the result of an increased distribution of alpha-linolenic acid, due to its amphipathic nature, to the increased oil-water interface.

Administration, Oral↗

The influence of charged lipids on the flocculation and coalescence of oil-in-water emulsions. I: Kinetic assessment of emulsion stability.

The influence of various negatively charged lipids on the stability of phospholipid stabilized oil-in-water emulsions in the presence of varying concentrations of calcium chloride was examined by a measurement of the changes in the turbidity of the emulsion over time. The data were described well by the following equation: (Ai - A) = (Ai - A0) exp(-kt) where Ai is the maximum spectrophotometric absorbance achieved in the system, A is the absorbance at time t, A0 is the absorbance at the start of the experiment and k is the flocculation or coalescence rate constant. Plots of k and Ai/A0 vs. concentration of Ca++ provided an indication of the rate and extent of emulsion flocculation/coalescence, respectively. The sodium salts of phosphatidic acid (SPA) and oleic acid (SO) increased the critical flocculation concentration of calcium while sodium phosphatidylinositol (SPI) and sodium phosphatidylserine (SPS) had no effect on the critical flocculation concentration compared to the control emulsion. The addition of all lipid salts increased the rate of flocculation compared to the control emulsion, however, emulsions containing SPI demonstrated the highest values of k. In contrast, emulsions containing SO coalesced to the largest extent, as indicated by large values of Ai/A0. Systems containing charged phosphatides regained some stability in higher concentrations of Ca++ while those containing oleate were comparatively more unstable up to 20 mM Ca++. Based upon the results of the present studies, it appears that phosphatidic acid is the most important fraction of the anionic phosphatides in stabilizing an emulsion in the presence of calcium ion.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Stability↗

A method for the characterization of emulsions, thermogranulometry: application to water-in-crude oil emulsion.

Emulsions are used in a wide range of applications and industries. Their size distribution is an important parameter because it influences most of the emulsion properties of emulsions. Several techniques of characterization are used to determine the granulometric distribution of emulsions, but they are generally limited to dilute samples and are based on complex algorithms. We describe a method that allows characterization of the droplet size distribution of emulsions using thermal analysis (thermogranulometry). This method permits the use of very concentrated samples without any dilution or perturbation of the system. We first define our method by a thermodynamic and kinetic approach. We studied a real system, i.e., crude oil emulsions, which form very concentrated, viscous, and opaque emulsions with water. We present a correlation between the size of droplets and their freezing temperature, corresponding to our system. Then we compare the size distributions obtained by our method with those derived by direct microscopy observations. The results obtained show that thermogranulometry may be an interesting method of characterization of emulsions, even for concentrated systems.

Journal Article↗

Partition of antimicrobial additives in an intravenous emulsion and their effect on emulsion physical stability.

A number of antimicrobial agents are potentially applicable to the preservation of small-volume parenteral emulsions. However, the physical stability of these emulsions is of paramount importance in ensuring their safety, and it is possible that antimicrobial additives could reduce the emulsion stability by a number of mechanisms. We have studied the effects of several antimicrobial agents on the physical stability of Diprivan, an intravenous anaesthetic emulsion. A particular problem is that many antimicrobial additives require an acidic pH in order to be effective (e.g. sodium benzoate, sodium metabisulphite) and the emulsion surface potential is insufficient to stabilize the emulsion to coalescence under these conditions. In addition several antimicrobial agents (e.g. methyl paraben and benzoic acid) partition into the oil phase of the emulsion, requiring the use of increased concentrations to remain effective. We describe an assay technique to quantify the oil partition, liposomal partition, and droplet surface adsorption of the additives. This illustrates that significantly more additive is partitioned out of the water phase than might be predicted from simple oil/water partition experiments.

Anti-Infective Agents↗

Lipid oxidation in emulsions as affected by charge status of antioxidants and emulsion droplets.

The influence of charge status of both lipid emulsion droplets and phenolic antioxidants on lipid oxidation rates was evaluated using anionic sodium dodecyl sulfate (SDS) and nonionic polyoxyethylene 10 lauryl ether (Brij)-stabilized emulsion droplets and the structurally similar phenolic antioxidants gallamide, methyl gallate, and gallic acid. In nonionic, Brij-stabilized salmon oil emulsions at pH 7.0, gallyol derivatives (5 and 500 microM) inhibited lipid oxidation with methyl gallate > gallamide > gallic acid. In the Brij-stabilized salmon oil emulsions at pH 3.0, low concentrations of the galloyl derivatives were prooxidative or ineffective while high concentrations were antioxidative. In SDS-stabilized salmon oil emulsions, oxidation rates were faster and the galloyl derivatives were less effective compared to the Brij-stabilized emulsions. Differences in antioxidant activity were related to differences in the ability of the galloyl derivatives to partition into emulsion droplets and to increase the prooxidant activity of iron at low pH.

Animals↗

Studies on the adjuvant effect of water-in-oil-in-water (w/o/w) emulsion of sesame oil. 1. Enhanced and persistent antibody formation by antigen incorporated into the water-in-oil-in-water emulsion.

Water-in-oil-in-water (w/o/w) emulsion developed in our laboratory is as effective as water-in-oil (w/o) emulsion of Freund's incomplete adjuvant (FIA) in the stimulation of antibody formation. The emulsion is prepared by redispersion of water-in-sesame oil emulsion of an antigen solution in phosphate buffered saline with emulsifier, Tween 80. The emulsion can be stored at 4 degrees C for at least 3 months without any evidence of change in the adjuvanticity and in the w/o/w state. Even a single injection of bovine serum albumin (BSA) in the w/o/w emulsion elicited a high antibody response in mice over the period of almost whole lifespan. 10 microgram BSA in w/o/w could stimulate antibody formation up to 2(12) in hemagglutination titer, while the same dose in free solution did not elicit any detectable antibody. The tissue reactions caused by the w/o/w emulsion at the injected site and in the regional lymph nodes were much less prominent than those by FIA.

Adjuvants, Immunologic↗

Effects of single application of a moisturizer: evaporation of emulsion water, skin surface temperature, electrical conductance, electrical capacitance, and skin surface (emulsion) lipids.

Effects of single application of an oil in water emulsion were studied on the forearm skin of 12 healthy volunteers. Five different non-invasive methods were used. Values were followed for 360 min after application of the emulsion, with the contralateral forearm as untreated control. The evaporation of emulsion water from the skin surface immediately rose to high values, but within 15 min returned to the original level. A parallel initial increase in conductance was observed; however, this was followed by a slightly increased level throughout the 360 min study. Electrical capacitance was also slightly increased throughout the study. Skin surface lipids, dominated by emulsion lipids, were increased, with high values for at least 120 min, followed by a gradual decline toward normal. Single application of emulsion is characterized by an initial evaporation phase, with evaporation of emulsion water, which lasts less than 15 min, followed by a lipidization phase, which lasts at least 360 min, dominated by the oil-constituent of the emulsion undergoing epidermal absorption. During the lipidization phase, epidermal hydration parameters are slightly but consistently improved.

Aged↗