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At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1978

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↗
PubMed1992

Novel affinity separations based on perfluorocarbon emulsions. Use of a perfluorocarbon affinity emulsion for the purification of human serum albumin from blood plasma in a fluidised bed.

A perfluorocarbon affinity emulsion has been generated by homogenisation of a saturated perfluorocarbon oil with a polymeric fluorosurfactant based on poly(vinyl alcohol) (relative molecular mass 9000-10,000) previously derivatised with the triazine dye CI Reactive Blue 4. This affinity emulsion has subsequently been cross-linked in situ and used in a fluidised bed for the purification of human serum albumin (HSA) from blood plasma. HSA was quantitatively recovered in a semi-continuous fashion from plasma at an average purity of 90 +/- 3.3%. The albumin binding capacity of the emulsion has been shown to be 0.59 mg/ml by frontal analysis corresponding to a mol/mol ligand usage of 13.5%. In all regards, when used in a fluidised bed, the emulsions have been shown to behave as a normal chromatographic material. They are stable under operational conditions with no coalescence being observed for periods greater than 1 year. These novel liquid affinity supports present an exciting opportunity to develop a range of unit operations for the continuous purification of proteins.

Chromatography, Affinity↗
PubMedDate not supplied

Preparation of multi-phase microspheres of poly(D,L-lactic acid) and poly(D,L-lactic-co-glycolic acid) containing a W/O emulsion by a multiple emulsion solvent evaporation technique.

Multi-phase microspheres of poly(D,L-lactic acid) (PLA) or poly(D,L-lactic-co-glycolic acid) (PLGA) containing a water-in-oil (W/O) emulsion were prepared by a multiple emulsion solvent evaporation technique. Acetonitrile was used as the solvent for the polymers and light mineral oil as the dispersion medium for the encapsulation procedure. Process and formulation parameters to optimize the microencapsulation of a W/O emulsion containing water-soluble drugs were investigated. Drug loading efficiencies of 80-100 per cent were obtained under specific preparative conditions. The drug loading efficiency in the microspheres was dependent upon the ratio of the W/O emulsion to polymer and the concentration of surfactant in the mineral oil. Compared to conventional microspheres, in which fine drug particles are homogeneously dispersed in the polymer beads, the multi-phase microspheres permit the higher encapsulation efficiency of water-soluble drugs and eliminate partitioning into the polymer-acetonitrile phase which results in low encapsulation efficiency with conventional solvent evaporation techniques.

Acetonitriles↗
PubMed1978

Studies on the adjuvant effect of water-in-oil-in-water (w/o/w) emulsion of sesame oil. 2. Mode of action of the w/o/w emulsion.

The water-in-oil-in-water (w/o/w) emulsion showed potent adjuvant effect on the antibody formation to thymus-dependent antigens, but not to thymus-independent antigens. In hapten-carrier system the priming with carrier in the w/o/w emulsion enhanced more effectively the carrier specific helper function than did the priming with carrier in free solution. The cells responsible for the helper function were radioresistant. In the adoptive cell transfer system, the w/o/w emulsion was shown to enhance helper cell function. It is discussed that our w/o/w emulsion exerts the adjuvant effect by enhancing helper T cell activity.

Adjuvants, Immunologic↗
PubMed1992

Effects of sphingomyelin and phosphatidylcholine acyl chains on the clearance of triacylglycerol-rich lipoproteins from plasma. Studies with lipid emulsions in rats.

Series of lipid emulsions were prepared as physical models of lymph chylomicrons. The emulsion phospholipid was systematically varied with respect to sphingomyelin, in 0-100% mixtures with egg yolk phosphatidylcholine (EYPC). In other emulsions, the phospholipid was systematically varied with respect to dipalmitoylphosphatidylcholine (DPPC) in 0-100% mixtures with 1-palmitoyl-2-oleoylphosphatidylcholine (POPC). All emulsions contained unlabeled free cholesterol, radiolabeled triolein (TO) and radiolabeled cholesteryl oleate (CO). The emulsions were injected into conscious rats to measure the clearances of emulsion TO and CO and the capture of lipid radioactivity by selected organs. The emulsions containing EYPC or POPC were metabolized similarly to lymph chylomicrons, consistent with rapid lipoprotein lipase-mediated hydrolysis of emulsion TO followed by hepatic uptake of the CO in the triglyceride-depleted emulsion remnants. Emulsions stabilized with either 1-oleoyl-2-stearoyl- or 1-stearoyl-2-oleoylphosphatidylcholine (OSPC or SOPC) were metabolized similarly. Increasing amounts of sphingomyelin in EYPC emulsions progressively slowed the removal of TO and CO labels from plasma. With 50% sphingomyelin clearance was very slow, while emulsion clearance was negligible with 100% sphingomyelin. Emulsions containing 20% of DPPC in POPC were metabolized similarly to 100% POPC, but 40% or more of DPPC progressively slowed the removal from plasma of both TO and CO. With 100% DPPC clearance was characterized by a rapid initial removal of about 30% of the injected material, followed by a second phase when removal was negligible, suggesting lack of hydrolysis of triacylglycerols by lipoprotein lipase. Changes in the apolipoproteins associated with the emulsions probably mediated the observed changes in clearance.

Animals↗
PubMed1992

Oral delivery of a renin inhibitor compound using emulsion formulations.

The oral delivery of O-(N-morpholino-carbonyl-3-L-phenylaspartyl-L- leucinamide of (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylhetane (I), a new renin inhibitor, was studied in the in vivo rat model using emulsion formulations. The components of the emulsion formulations were chosen based on their proposed effects on membrane structure, membrane fluidity, and solute transport. The percent absolute bioavailability (%AB) of I was increased from 0.3% (water suspension) to 5.1% when long-chain unsaturated fatty acid (oleic acid, linoleic acid, etc.)- and mono- and diglyceride (monolein, dilaurin, etc.)-containing emulsion formulations were used. Considering very high first-pass liver extraction of the compound (80%), it is suggested that emulsion formulations increased the intestinal transport of the compound significantly. The solubility of I in aqueous media with and without bile salt (20 mM) was found to be low (approximately 1 micrograms/ml). Incubation in 0.01 N HCl did not affect the particle size of the emulsion. The titration of oleic acid/monoolein emulsion in a pH 6.5 medium with a mixed bile salt system indicated reduction in the particle size of the emulsion. Drug precipitation was observed above 30 mM bile salt concentrations. No drug crystals could be detected in the intestinal contents of the rats when emulsion formulations were ingested. These results suggest that in the intestine of the animals, the particle size of the emulsions is reduced in the presence of bile fluid while the drug resides primarily in the oil phase. The mechanism of enhanced transport of I from the emulsion formulations is discussed along with the possibility of cotransport for the drug and oil. Emulsion formulations can be a potential delivery form for low-bioavailable lipid-soluble drugs.

Absorption↗
PubMed1992

Effect of liposomal content of lipid emulsions on plasma lipid concentrations in low birth weight infants receiving parenteral nutrition.

We studied the effects of phospholipid liposomes present in intravenously administered lipid emulsions on plasma lipid levels in preterm infants given 10% and 20% lipid emulsions. Twenty premature infants (birth weight 1454 +/- 54 gm) on a parenteral nutrition regimen received up to 4 gm triglycerides per kilogram per day in a 20% lipid emulsion for 2 weeks, and then received the 10% emulsion at 2 gm triglycerides per kilogram per day, which delivered the same total phospholipid load but twice the amount of liposomes. Triglyceride, total cholesterol, and phospholipid concentrations increased significantly when the infants were given 2 gm triglycerides per kilogram per day in the 10% emulsion rather than 4 gm/kg per day in the 20% emulsion (44 +/- 4 to 57 +/- 5 mg/dl, 134 +/- 6 to 162 +/- 9 mg/dl, and 204 +/- 8 to 251 +/- 10 mg/dl, respectively). Lipoprotein analysis indicated the presence of lipoprotein X-like particles in the low-density lipoprotein fraction and an increase of the intermediate-density lipoprotein fraction in infants who received the 10% emulsion. The presence of excess phospholipids in the 10% emulsion was associated with greater plasma lipid alterations. Therefore the use of 20% rather than 10% emulsion allows for more efficient triglyceride clearance, even at a higher triglyceride intake. Administration of emulsions that are relatively poor in phospholipid liposomes may allow delivery of > 2 gm triglycerides per kilogram per day to low birth weight infants.

Cholesterol↗
PubMed1992

Trial of glucose versus fat emulsion in preparation of amphotericin for use in HIV infected patients with candidiasis.

OBJECTIVES: To compare the tolerance, efficacy, and pharmacokinetics of amphotericin deoxycholate (Fungizone) prepared in a parenteral fat emulsion (Intralipid 20%) or glucose in HIV patients with candidiasis. DESIGN: Non-blind randomised controlled trial. SETTING: University hospital; tertiary clinical care. PATIENTS: 22 HIV positive patients with oral candidiasis. INTERVENTIONS: Amphotericin 1 mg/kg/day given on four consecutive days as a one hour infusion dissolved in either 5% glucose (amphotericin-glucose) or parenteral fat emulsion at a final concentration of 2 g/l fat emulsion (amphotericin-fat emulsion). MAIN OUTCOME MEASURES: Clinical tolerance (fever, chills, sweats, nausea, arterial pressure, and pulse rate); biological tolerance (serum creatinine, electrolyte, and magnesium values); clinical score of candidiasis; and serum concentrations of amphotericin. RESULTS: 11 patients were enrolled in each group. All the amphotericin-fat emulsion infusions were given without serious problem whereas four amphotericin-glucose infusions were stopped because of renal impairment (n = 3) or severe chills (n = 2), or both. For patients completing the amphotericin-glucose treatment creatine concentration increased by 42 mumol/l; four of seven patients had at least one creatinine value > or = 133 mumol/l versus one of 11 receiving amphotericin-fat emulsion. Magnesium concentration fell significantly with amphotericin-glucose but not with amphotericin-fat emulsion. Clinical side effects were noted in 36/38 infusions with amphotericin-glucose but 10/44 with amphotericin-fat emulsion. Oral candidiasis score was reduced similarly in both groups. Serum amphotericin concentrations were significantly lower and the volume of distribution of the drug higher after infusion of amphotericin-fat emulsion than after amphotericin-glucose. CONCLUSIONS: Clinical and renal toxicity of amphotericin are reduced when the drug is prepared in fat emulsion. Preparation is simple and cost effective. Its efficacy is similar to that of conventional amphotericin.

AIDS-Related Opportunistic Infections↗
PubMed1975

Effect of fluorocarbon emulsions on the mechanical fragility of normal and sickle cells: in vitro studies.

Mechanical fragility measurements have been made in vitro on fluorocarbon emulsions mixed with normal and sickle cells in plasma to determine the effect of fluorocarbon. Emulsions of FC-80 with Pluronic F-68 were added to give final solutions of 0, 1, 5, 10, and 20% fluorocarbon emulsion. The effect of the fluorocarbon emulsion was observed in the presence and absence of oxygen. In the presence of oxygen, there was no effect of the fluorocarbon emulsion on the mechanical fragility of normal or sickle cells. In deoxygenated systems, however, there was significantly less hemoglobin in the plasma during the mechanical fragility test with fluorocarbon emulsion added to sickle cell blood. The normal blood was not affected by the fluorocarbon emulsion in the deoxygenated system. Five percent of fluorocarbon emulsion was required for a significant effect on the deoxygenated sickle cells. Since the effect of the fluorocarbon emulsion was in a deoxygenated condition, the effect is due to the presence of the fluorocarbon emulsion and not its oxygen carrying capability.

Anemia, Sickle Cell↗