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Effects of cholesterol and cholesteryl oleate on lipolysis and liver uptake of triglyceride/phosphatidylcholine emulsions in rats.

Emulsions composed of soy bean triglyceride (TG), egg yolk phosphatidylcholine (PC), cholesterol (Chol) or cholesteryl-oleate (CO), labeled with a cholesteryl ether (3H-CHE) and a triglyceride (14C-TO), were injected into rats. 14C-TO was removed from plasma faster than 3H-CHE. The 14C-labeled moiety is cleaved by digestion of the TG in the emulsion in plasma and is removed to the endothelial cells (lipolysis). In contrast, the 3H-label remains stably associated and represents circulating emulsion particles. The majority (90%) of the 3H-label disappearing from the plasma accumulated in the liver for all types of emulsions. On the basis of these observations, the lipolysis and the removal of emulsion particles to organs (mainly liver) were determined: 30 mole percent of cholesterol (Chol) at the TG-PC emulsion surface markedly retarded organ uptake, but the effect on lipolysis was rather small; 20 mole percent of cholesteryl oleate (CO) in the TG-PC emulsion cores delayed both organ uptake and lipolysis, and induced a rapid increase in organ uptake rate after the initial delay accompanying the gradual progress of lipolysis. Lipolysis led to the enrichment of the cores with CO. Replacement of the core TG by CO, however, induced strong suppression of the liver uptake. These results show that the lipid composition at both surface and core of emulsion particles is a crucial factor in metabolism in the rat.

Animals↗

Repair of acetone- and sodium lauryl sulphate-damaged human skin barrier function using topically applied emulsions containing barrier lipids.

BACKGROUND: It is generally acknowledged that well-formulated moisturizing skin care products can restore disturbed barrier function that can be assessed by transepidermal water loss (TEWL) measurements. When ceramides and/or other barrier lipids are incorporated, it is, however, not always clearly demonstrated which ingredients of the formulation exert the beneficial effects. OBJECTIVES: In this study the effects of topically applied ceramide-containing mixtures on the barrier repair of sodium lauryl sulphate (SLS)- and acetone-induced skin damage have been studied in human volunteers. TEWL and stratum corneum hydration measurements were carried out. The emulsions applied contained either a mixture of two types of ceramides, CerIII and CerIIIB (emulsion 1) or a complete mixture of ceramides III, IIIB and VI together with phytosphingosine, cholesterol and the free fatty acid linoleic acid (emulsion 2). RESULTS: After SLS damage, it was observed that barrier recovery was significantly accelerated by topical application (14 days, 2 x/d) of emulsion 2 compared with the results obtained with emulsion 1. Corneometrical results were not relevant due to the occurrence of scaly fissured skin, failing to provide a good skin/probe contact. Although no effect on TEWL could be observed, the improvement of skin hydration after acetone treatment and a single application of the emulsions, was significantly more positive for emulsion 2 than for emulsion 1. CONCLUSIONS: The investigative methods used in this study show that ceramides combined with other skin lipids can improve barrier repair after damage.

Acetone↗

Antioxidant status of surgical patients receiving TPN with an omega-3-fatty acid-containing lipid emulsion supplemented with alpha-tocopherol.

BACKGROUND: LCT lipid emulsions and even more fish oil-containing lipid emulsions are under debate regarding their tocopherol and PUFA content as well as their effect on the antioxidative status especially in patients with oxidative stress. METHODS: Thirty-three patients undergoing major abdominal surgery were randomly assigned to receive either an alpha-tocopherol-supplemented (562 micromol/l) MCT/LCT/omega-3-acid triglycerides (MLF, 5/4/1 w/w/w, 20%) emulsion or a soybean oil-based LCT emulsion (20%). The TPN regimen continuously provided 1.4 g fat kg bw(-1)d(-1)over 5 days. RESULTS: Plasma antioxidant concentrations were strongly reduced by surgical treatment. Following 5 days of TPN with the MLF emulsion, mean plasma alpha-tocopherol increased by 20.0 micromol/l (1.98 micromol/mmol lipid), while nearly no change was observed in the LCT emulsion group. In both groups, plasma concentrations of all non-supplemented antioxidants (vitamin C, carotenoids, selenium) as well as serum total antioxidant capacity further decreased during TPN. The concentrations of plasma cholesterol oxidation products as a measure of in vivo lipid peroxidation revealed no changes over the TPN period in either group. CONCLUSION: In contrast to the LCT emulsion, administration of the a-tocopherol supplemented MLF lipid emulsion normalized a-tocopherol plasma concentrations. Despite its high long-chain PUFA content, no hint for increased lipid peroxidation was found.

Abdomen↗

Lipid nano/submicron emulsions as vehicles for topical flurbiprofen delivery.

The application of lipid nano/submicron emulsions as topical drug carrier systems for the percutaneous absorption of flurbiprofen was investigated. The lipid emulsions were made up of isopropyl myristate (IPM), soybean oil, or coconut oil as the oil phase, egg lecithin as the predominant emulsifier, and double-distilled water as the external phase. Stearylamine (SA) and deoxycholic acid (DA) also were used to produce positively and negatively charged emulsions. To evaluate the physicochemical properties of the lipid emulsions, particle size by laser light scattering, the image of atomic force microscopy, and relaxation time values by Nuclear Magnetic Resonance (NMR) were determined. The in vitro permeation data showed that incorporation of SA significantly reduced the topical delivery of flurbiprofen. On the other hand, incorporation of DA exhibited no or a negligible effect on drug permeation. Enhancement of drug absorption was observed when adding oleic acid as part of the oil phase. The in vivo topical application of flurbiprofen from selected lipid emulsions showed a similar trend to the in vitro status. Furthermore, the intersubject variability was considerably reduced by lipid emulsions than by aqueous suspensions in both the in vitro and in vivo experiments. The irritant profiles of lipid emulsions showed that IPM elicited higher irritation than soybean oil. The incorporation of oleic acid also produced skin disruption. The results in the present study suggest the feasibility of lipid emulsions for the topical delivery of flurbiprofen.

Administration, Topical↗

Development of a novel parenteral formulation for tetrazepam using a lipid emulsion.

A novel parenteral formulation for tetrazepam (10 mg/ml) was developed using lipid emulsions. This formulation utilized a new lipid emulsion formulation, which was developed by changing the polarity of the oil phase. It was found that increasing the polarity of the oil phase resulted in enhanced solubility of tetrazepam. Tetrazepam showed higher solubility in a mixture of castor oil and middle-chain triglycerides (MCTs) (1:1) than in any other oil investigated. This mixture resulted in low interfacial tension and moderate viscosity, which seemed to be the optimum oil phase. In addition, to increase the concentration of tetrazepam, an emulsion formulation containing 30% oil phase was produced and optimized. The drug-free emulsion formulation showed fine particle sizes with an imperceptible change in physicochemical properties after more than 2 years on the shelf. As a result, it was possible to produce a parenteral emulsion formulation containing 10 mg/ml tetrazepam. No change in the physicochemical properties of the emulsion was observed after the addition of tetrazepam. The tetrazepam emulsion showed stable behavior during the autoclaving process and good shelf stability for at least 10 months as well. Tetrazepam itself also displayed good stability during the autoclaving process and also showed good shelf stability in this emulsion formulation.

Anti-Anxiety Agents↗

Influence of emulsion droplet surface charge on indomethacin ocular tissue distribution.

The aim of this study was to compare the corneal penetration of indomethacin from Indocollyre [a marketed hydro-poly(ethylene glycol) (PEG) ocular solution] to that of a negatively and a positively charged submicron emulsion. Male albino rabbits were separated randomly into three groups and each group (N = 15) was treated with either one drop of radiolabeled 0.1% Indocollyre, or 0.1% indomethacin positively or negatively charged submicron emulsion, respectively. The rabbits were sacrificed at selected time points and the eyes were enucleated. The eyes were dissected into the different tissues: cornea, conjunctiva, aqueous humor, iris, lens, vitreous, sclera, and retina. The samples were weighed before radioactivity counting. Regardless of the preparation instilled, the highest concentration of indomethacin was achieved in the cornea followed by conjunctiva, sclera retina, and aqueous humor. However, the positively charged emulsion provided significantly higher drug levels than the control solution and negatively charged emulsion only in the aqueous humor and sclera-retina. Furthermore, the spreading coefficient of the positively charged emulsion on cornea is four times higher than that of the negatively charged emulsion. It was therefore deduced that the positively charged submicron emulsions have better wettability properties on the cornea compared to either saline or the negatively charged emulsion. The positive charge may prolong the residence time of the drop on the epithelial layer of the cornea and thus enable better drug penetration through the cornea to the internal tissues of the eye, as confirmed by the animal studies.

Absorption↗

Pilocarpine incorporated into a submicron emulsion vehicle causes an unexpectedly prolonged ocular hypotensive effect in rabbits.

Pilocarpine, a widely used antiglaucoma drug, was incorporated into a newly developed submicron emulsion (pilocarpine emulsion) suitable for local ocular administration. Pilocarpine-Emulsion effect on the intraocular pressure (IOP) was studied following a single dose application in normotensive rabbits. Membrane filtration (steam autoclaving) was found not to affect particle size distribution, zeta potential or pH of the pilocarpine emulsion preparation. A single dose application of pilocarpine emulsion 1.7% (equivalent to 2% pilocarpine hydrochloride) induced a prolonged progressive decrease in IOP in normotensive rabbits, which started at eleven hours post instillation and reached its maximal value of 6.0 +/- 0.2 mmHg at 29 hours. The pressure decreasing effect induced by pilocarpine emulsion treatment followed a pattern different from that generated by generic pilocarpine (Pilocarpine Hydrochloride 2% eye drops); In the latter group, IOP reduction (starting at two hours) persisted during the initial five hours post-instillation, while in the former, the hypotensive effect started at a later stage, and was maintained during a twenty nine hour follow-up causing a greater IOP decrease than in the generic group (% delta IOP of 28.5% and 18%, respectively). In the contralateral eyes of Pilocarpine Emulsion treated rabbits, an ocular hypotensive effect was noted late after application (11 hours through 29 hours post-instillation), while this effect was negligible in rabbits-treated with aqueous pilocarpine. Our findings point to the possibility that the novel preparation of pilocarpine incorporated into submicron emulsion might serve as a long-acting form of pilocarpine which might require a single daily application. Further studies are required to elucidate the mechanism and action of this preparation.

Administration, Topical↗

Digestion and absorption of 2 fat emulsions with different droplet sizes in the human digestive tract.

BACKGROUND: The extent of fat emulsification affects the activity of digestive lipases in vitro and may govern digestion and absorption of dietary fat. OBJECTIVE: We investigated the effect of the fat globule size of 2 enteral emulsions on fat digestion and assimilation in humans. DESIGN: Healthy subjects received intragastrically a coarse (10 microm) and a fine (0.7 microm) lipid emulsion of identical composition in random order. Gastric and duodenal aspirates were collected throughout digestion to measure changes in fat droplet size, gastric and pancreatic lipase activities, and fat digestion. Blood lipids were measured postprandially for fat assimilation. RESULTS: Despite an increase in droplet size in the stomach (2.75-6.20 microm), the fine emulsion retained droplets of smaller size and its lipolysis was greater than that of the coarse emulsion (36.5% compared with 15.8%; P < 0.05). In the duodenum, lipolysis of the fine emulsion was on the whole higher (73.3% compared with 46.3%). The overall 0-7-h plasma and chylomicron responses given by the areas under the curve were not significantly different between the emulsions, but the triacylglycerol peak was delayed with the fine emulsion (3 h 56 min compared with 2 h 50 min). CONCLUSIONS: Fat emulsions behave differently in the digestive tract depending on their initial physicochemical properties. A lower initial fat droplet size facilitates fat digestion by gastric lipase in the stomach and duodenal lipolysis. Overall fat assimilation in healthy subjects is not affected by differences in initial droplet size because of efficient fat digestion by pancreatic lipase in the small intestine. Nevertheless, these new observations could be of interest in the enteral nutrition of subjects suffering from pancreatic insufficiency.

Absorption↗

An emulsion formulation of amphotericin B improves the therapeutic index when treating systemic murine candidiasis.

Incorporating amphotericin B into liposomes was reported to decrease amphotericin B toxicity without a concomitant loss of antifungal efficacy. We formulated an alternative emulsion-based delivery system for amphotericin B and compared it with Fungizone. The maximal tolerated dose (MTD) in mice was 1 mg of Fungizone/kg; however, the MTD was greater than 9 mg of the Intralipid emulsion formulation/kg. The emulsion formulation and Fungizone were equipotent for treating systemic candidiasis in mice. Amphotericin B nephrotoxicity, as manifested by polyuria that was resistant to antidiuretic hormone, was markedly diminished when amphotericin B was administered as an emulsion to rats. Loss of potassium from human red blood cells was also reduced by formulating this agent within emulsions. The emulsion formulation extended the survival time of mice that had established Candida albicans infections, when compared with the Fungizone treatment. The efficacy and reduced toxicity of the amphotericin B emulsion are findings suggesting that the emulsion formulation is preferable to Fungizone.

Amphotericin B↗

In-vitro and in-vivo studies of the decrease of amphotericin B toxicity upon association with a triglyceride-rich emulsion.

The effects of amphotericin B associated with a triglyceride-rich emulsion (AB-emulsion), shown previously to behave like lymph chylomicrons, were evaluated in vitro and in vivo. Incorporation of amphotericin B to the emulsion was monitored by UV-visible spectrophotometry. Whilst conventional amphotericin B induced a considerable K+ efflux from erythrocytes, AB-emulsion had essentially no effect. In contrast, the K+ efflux from Candida albicans was similar upon incubation either with AB-emulsion or with conventional amphotericin B. Administration to rats showed reduced mortality due to AB-emulsion compared with conventional amphotericin B. Renal toxicity was also decreased upon AB-emulsion treatment, as evaluated by serum urea and creatinine levels. These data suggest that chylomicron-like emulsions could be utilized as vehicles for amphotericin B in antifungal therapy.

Amphotericin B↗

Activation of neuronal N-methyl-D-aspartate receptor channels by lipid emulsions.

UNLABELLED: Lipid emulsions are widely used as carriers for hypnotics such as propofol, etomidate, and diazepam. It is assumed that the emulsions alone exert no effect on cellular functions nor influence the pharmacokinetics, pharmacodynamics, or anesthetic and analgetic potency of the hypnotics they carry. To elucidate possible interactions between lipid emulsions and cell membranes, in particular membrane-bound proteins, we investigated the effects of commercially available lipid emulsions on the cell membranes of cultured cortical neurons from the mouse by using the whole-cell configuration of the patch-clamp technique. Of nine lipid emulsions tested, three, i.e., Intralipid, Structolipid, and, to a much lesser extent, Abbolipid, activated membrane currents in the neuronal cells in a dilution-dependent manner. The emulsion-induced currents were not affected by picrotoxin or bicuculline but were inhibited by DL-AP5 and ketamine. The voltage dependence of the currents was influenced by the presence of Mg(2+) in a way that is typical for currents conducted by N-methyl-D-aspartate receptor channels. We conclude that Intralipid, Structolipid, and Abbolipid activate N-methyl-D-aspartate receptor channels in cortical neurons. IMPLICATIONS: Lipid emulsions are widely used as carriers for hypnotics such as propofol, etomidate, or diazepam. We tested nine commercially available lipid emulsions and demonstrate that three of them--Intralipid, Structolipid, and Abbolipid--activate NMDA receptor channels in the membranes of cortical neuronal cells.

2-Amino-5-phosphonovalerate↗

Effect of stabilized iodized oil emulsion on experimentally induced hepatocellular carcinoma in rats.

PURPOSE: Previous studies have shown that the use of Lipiodol UltraFluid (LUF) emulsified with water leads to an increase in the tumoral uptake of iodine I 131-labeled LUF and reduced pulmonary uptake. Although emulsions containing LUF are currently used for chemoembolization of hepatocellular carcinomas (HCCs), this approach is impossible with intraarterial radiation therapy (RT) because of the problems of radiation protection linked to instability of the emulsions. The aims of this study were to develop stabilized emulsions of radiolabeled LUF of different particle sizes and viscosities and to study its biodistribution in rats with HCC. MATERIALS AND METHODS: An emulsifier made of polyethylene glycol and hydrogenated castor oil was used to stabilize emulsions containing water and technetium Tc 99m-labeled Super Six Sulfur LUF. The various emulsions were injected in the hepatic arteries of rats with HCC. Twenty-four hours after injection, the rats were killed and the liver, tumor, and lungs were removed to perform ex-vivo gamma-counting to quantify tumoral, hepatic, and pulmonary uptake. RESULTS: Emulsions of oil in water and water in oil of different viscosities (0.68-1.06 Pa.S) and particle size distributions (21-45 mum) were prepared and kept stable for more than 24 hours. Whatever the type of emulsion, the observed effect on tumoral uptake was the opposite of that expected. Indeed, a decrease in tumoral activity was observed (P < .05 in three of five cases) and a tendency toward increased pulmonary activity was observed (P < .05 in two of five cases) rather than any significant decrease. CONCLUSIONS: This study made it possible to develop emulsions of radiolabeled iodized oil that remain stable for more than 24 hours. However, studies of biodistribution in rats with HCC failed to demonstrate any improvement in tumoral targeting, but rather showed a decrease in tumoral uptake that renders this approach impractical for intraarterial radiolabeled iodized oil RT as well as for intraarterial iodized oil chemoembolization. These results may possibly be explained by the use of an emulsifier containing lipophilic and hydrophilic components that modify the properties of LUF.

Animals↗

Plasma clearance of emulsified triolein in conscious rats: effects of phosphatidylcholine species, cholesterol content and emulsion surface physical state.

In vivo clearance of an emulsified triglyceride from rat plasma is strongly influenced by the phosphatidylcholine molecular species and the cholesterol content of the emulsion. Chylomicron-sized, glycerol-tri[9,10-3H]oleate (triolein)-sonicated emulsions containing 2-3 or 9-14 mol% unesterified cholesterol and specific phosphatidylcholines (egg, dimyristoyl, dipalmitoyl, distearoyl) were prepared above the phospholipid gel----liquid crystalline transition temperatures and injected intravenously into awake, non-fasting rats in bolus doses of 1-3 mg lipid. The emulsified triolein was cleared from plasma both by lipolysis during circulation and by uptake of emulsion particles or their remnants into tissues. Increasing the cholesterol content greatly accelerated particle clearance from plasma when emulsions were made with mixed-chain (egg) phosphatidylcholine, but prolonged their circulation time when the emulsions contained saturated phosphatidylcholines. The relative amounts cleared by reticuloendothelial versus liver parenchymal cells were influenced both by the cholesterol content and the phosphatidylcholine species of the emulsions. Significant triolein lipolysis in plasma occurred only with egg or dimyristoyl phosphatidylcholine emulsions containing 2-3% cholesterol and this lipolysis was blocked by increasing the cholesterol content. No lipolysis occurred when emulsions contained dipalmitoyl or distearoyl phosphatidylcholine, irrespective of cholesterol content.

Animals↗

Amphotericin B in children with malignant disease: a comparison of the toxicities and pharmacokinetics of amphotericin B administered in dextrose versus lipid emulsion.

In a prospective, randomized clinical trial, the toxicity of 1 mg of amphotericin B (AmB) per kg of body weight per day infused in 5% dextrose was compared with that of AmB infused in lipid emulsion in children with malignant disease. In an analysis of 82 children who received a full course of 6 days or more of AmB (117 courses), it was shown that there were significant increases in plasma urea and creatinine concentrations and in potassium requirement after 6 days of therapy with both AmB infused in dextrose and AmB infused in lipid emulsion, with there being no difference between the two methods of AmB administration. An intent-to-treat comparison of the numbers of courses affected by acute toxicity (fever, rigors) and chronic toxicity (nephrotoxicity) also indicated that there was no significant difference between AmB infused in dextrose (78 courses) and AmB infused in lipid emulsion (84 courses). The pharmacokinetics of AmB were investigated in 20 children who received AmB in dextrose and 15 children who received AmB in lipid emulsion. Blood samples were collected up to 24 h after administration of the first dose, and the concentration of AmB in plasma was analyzed by a high-performance liquid chromatography assay. The clearance (CL) of AmB in dextrose (0.039 +/- 0.016 liter. h-1. kg-1) was significantly lower (P < 0.005) than the CL of AmB in lipid emulsion (0.062 +/- 0. 024 liter. h-1. kg-1). The steady-state volume of distribution for AmB in dextrose (0.83 +/- 0.33 liter. kg-1) was also significantly lower (P < 0.005) than that for AmB in lipid emulsion (1.47 +/- 0.77 liter. kg-1). Although AmB in lipid emulsion is apparently cleared faster and distributes more widely than AmB in dextrose, this study did not reveal any significant advantage with respect to safety and tolerance in the administration of AmB in lipid emulsion compared to its administration in dextrose in children with malignant disease.

Adolescent↗

A submicron emulsion as ocular vehicle for delta-8-tetrahydrocannabinol: effect on intraocular pressure in rabbits.

delta 8-Tetrahydrocannabinol (delta 8-THC), a known antiglaucoma lipophilic drug, was incorporated in a submicron emulsion for ocular administration. The mean droplet size of the emulsion was 130 +/- 41 nm, and no droplet was larger than 400 nm. No change in pH, particle size distribution or zeta potential was noted after sterilization by steam autoclaving or long-term storage over 9 months. An intense and long-lasting intraocular pressure (IOP)-depressant effect was observed after ocular application (50 microliters) of the THC emulsion, 0.4% (w/w), to rabbits with ocular hypertension (chymotrypsin model). Lesser effects were observed in normotensive rabbits. No irritation effect of either the emulsion vehicle or THC emulsion on the rabbit eyes was detected. These results underline the promising properties of submicron emulsions as vehicles for lipophilic ophthalmic drugs. The mechanism by which the emulsion induced the marked delta 8-THC antiglaucoma effect remains unclear. However, the possible involvement of delta 8-THC systemic absorption in the hypotensive effect induced by the emulsion cannot be excluded and will be the subject of further investigation.

Animals↗

Effects of 2 lipid emulsions (LCT versus MCT/LCT) on the fatty acid composition of plasma phospholipid: a double-blind randomized trial.

BACKGROUND: Fatty acids from the diet or from IV fat emulsions are incorporated into the plasma and cell membrane phospholipids and act as substrates in the synthesis of eicosanoids. This study reports the effect of 2 parenteral lipid emulsions in plasma phospholipids fatty acids. METHODS: A total of 83 patients aged 18 to 75 years were randomized to receive long-chain triglycerides (LCT) or 50/50 mix of long- and medium-chain triglyceride emulsion (LCT/MCT). Blood samples were collected at baseline and at weekly intervals for 28 days. Plasma phospholipid fatty acids were measured by gas chromatography. RESULTS: Patients receiving LCT versus MCT/LCT emulsion have an increase in 18:2n6 and a decrease in 20:4n6 and 22:4n6 after 7, 14, and 21 days of treatment with parenteral nutrition. Phospholipid fatty acids at 15 days of treatment with parenteral nutrition with LCT versus MCT/LCT for 18:2n6 were 17.30% versus 22,90% (p < .05), for 20:4n6 10.44% versus 8.38% (p < .05), and for 22:4n6 0.51% versus 0.40% (p < .05). The 20:4n6 percentage inversely correlated with the percentage of 18:2n6 on days 7, 14, and 21: regression coefficients: -7.40 (p < .001), -7.39 (p < .001), and 5.70 (p < .001), respectively. CONCLUSIONS: Parenteral lipid emulsions modify fatty acid profiles in plasma phospholipids. MCT/LCT emulsions produce in phospholipids a fatty-acid profile that is closer to normality than that achieved with LCT emulsions. These changes in phospholipid fatty acids are suggestive of an inhibition of A-5-desaturase in patients who received LCT emulsions.

Adolescent↗

Comparative study of clearance of 10% and 20% fat emulsion.

The rate of fat emulsion clearance from the blood of 10 healthy adult male volunteers administered 0.1 gram of fat per kilogram body weight as 10% or 20% safflower oil emulsion (Liposyn) was studied. The subjects were hospitalized for 2 days and each was given the predetermined amount of one of the two fat emulsions (10% or 20%) by rapid injection into a peripheral vein and the rate of clearance of the emulsion determined over a 60-minute period, beginning when half of the emulsion had been injected. There was no significant difference in the clearance rate between the two emulsions. It is concluded that 20% fat emulsion is a safe as 10% fat emulsion for use in intravenous nutritional support.

Adult↗

Comparison of bone marrow toxicity of medium-chain and long-chain triglyceride emulsions: an in vitro study in humans.

BACKGROUND: In this study, we evaluated the in vitro bone marrow toxicity of two lipid emulsions containing either long-chain triglycerides (LCT) or a mixture of medium-chain triglycerides (MCT) and LCT. METHODS: Bone marrow cells were obtained from six healthy subjects and were cultured for 14 days after a 24-hour preincubation with various concentrations (from 0 to 10 mg/mL) of LCT- and LCT/MCT-based lipid emulsions. RESULTS: Compared with controls (no preincubation with lipid emulsion), both lipid emulsions significantly inhibited by 50% to 70% colony formation of all the human bone marrow cells cultured from a triglyceride concentration of 0.5 mg/mL (p < .05). Erythroid burst-forming unit (BFU-E) formation was significantly more inhibited with LCT/MCT emulsion than with LCT emulsion (p < .05). The inhibition of granulocyte-macrophage colony-forming unit (GM-CFU) and mixed granulocyte-erythrocyte-monocyte-megakaryocyte colony-forming unit (GEMM-CFU) formation did not significantly differ with the two emulsions. CONCLUSIONS: Both LCT- and LCT/MCT-based lipid emulsions strongly inhibit colony formation by human bone marrow cells. BFU-E colony formation is more sensitive to LCT/MCT inhibition than to LCT.

Adult↗