Medium-chain Triglyceride Emulsion Research Articles

The role of nutrition in analysis of risk factors and short-term outcomes for late-onset necrotizing enterocolitis among very preterm infants: a nationwide, multicenter study in China

BackgroundNecrotizing enterocolitis (NEC) is a serious gastrointestinal disease, primarily affects preterm newborns and occurs after 7 days of life (late-onset NEC, LO-NEC). Unfortunately, over the past several decades, not much progress has been made in its treatment or prevention. This study aimed to analyze the risk factors for LO-NEC, and the impact of LO-NEC on short-term outcomes in very preterm infants (VPIs) with a focus on nutrition and different onset times.MethodClinical data of VPIs were retrospectively collected from 28 hospitals in seven different regions of China from September 2019 to December 2020. A total of 2509 enrolled VPIs were divided into 2 groups: the LO-NEC group and non-LO-NEC group. The LO-NEC group was divided into 2 subgroups based on the onset time: LO-NEC occurring between 8 ~ 14d group and LO-NEC occurring after 14d group. Clinical characteristics, nutritional status, and the short-term clinical outcomes were analyzed and compared among these groups.ResultsCompared with the non-LO-NEC group, the LO-NEC group had a higher proportion of anemia, blood transfusion, and invasive mechanical ventilation (IMV) treatments before NEC; the LO-NEC group infants had a longer fasting time, required longer duration to achieve the target total caloric intake (110 kcal/kg) and regain birthweight, and showed slower weight growth velocity; the cumulative dose of the medium-chain and long-chain triglyceride (MCT/LCT) emulsion intake in the first week after birth was higher and breastfeeding rate was lower. Additionally, similar results including a higher proportion of IMV, lower breastfeeding rate, more MCT/LCT emulsion intake, slower growth velocity were also found in the LO-NEC group occurring between 8 ~ 14d when compared to the LO-NEC group occurring after 14 d (all (P < 0.05). After adjustment for the confounding factors, high proportion of breastfeeding were identified as protective factors and long fasting time before NEC were identified as risk factors for LO-NEC; early feeding were identified as protective factors and low gestational age, grade III ~ IV neonatal respiratory distress syndrome (NRDS), high accumulation of the MCT/LCT emulsion in the first week were identified as risk factors for LO-NEC occurring between 8 ~ 14d. Logistic regression analysis showed that LO-NEC was a risk factor for late-onset sepsis, parenteral nutrition-associated cholestasis, metabolic bone disease of prematurity, and extrauterine growth retardation.ConclusionActively preventing premature birth, standardizing the treatment of grade III ~ IV NRDS, and optimizing enteral and parenteral nutrition strategies may help reduce the risk of LO-NEC, especially those occurring between 8 ~ 14d, which may further ameliorate the short-term clinical outcome of VPIs.Trial registrationChiCTR1900023418 (26/05/2019).

Fish oil fat emulsion alleviates traumatic brain injury in mice by regulation of microglia polarization

Microglia activation, a hallmark of brain neuroinflammation, contributes to the secondary damage following traumatic brain injury (TBI). To explore the potential roles of different fat emulsions-long chain triglyceride (LCT) / medium chain triglyceride (MCT) and fish oil (FO) fat emulsion in neuroprotection and neuroinflammation in TBI, in this study, we first generated the controlled cortical impact (CCI) model of TBI mice. Then either LCT/MCT or FO fat emulsion treated mice were studied by Nissl staining to assess the lesion volume. Sham and TBI mice treated with 0.9% saline were used as controls. The fatty acid composition in different TBI mouse brains was further evaluated by gas chromatography. Immunofluorescent staining and quantitative RT-PCR both demonstrated the suppression of pro-inflammatory microglia and upregulated anti-inflammatory microglia in FO fat emulsion treated TBI brain or primary microglia induced by lipopolysaccharide (LPS) in vitro. Furthermore, motor and cognitive behavioral tests showed FO fat emulsion could partially improve the motor function in TBI mice. Together, our results indicate that FO fat emulsion significantly alleviates the TBI injury and neuroinflammation probably by regulating microglia polarization.

Effect of Oil Type on Spatial Partition of Resveratrol in the Aqueous Phase, the Protein Interface and the Oil Phase of O/W Emulsions Stabilized by Whey Protein and Caseinate.

Oil-in-water emulsions contain the inner oil phase, the protein membrane at the interface and the aqueous phase. In this study, the spatial partition of resveratrol was investigated in sunflower oil, fish oil, medium-chain triglyceride (MCT) and peppermint oil emulsions stabilized by native whey protein isolate (WPI), heat-denatured WPI and sodium caseinate. Resveratrol was added in the aqueous phase of emulsions and its partition was analyzed in term of resveratrol solubility in bulk oil and in the aqueous phase of protein, protein concentration and interfacial protein. The final concentrations of resveratrol in the aqueous phase were basically greater than those in the oil phase of fish oil, sunflower oil and MCT oil emulsions, while the final concentrations of resveratrol in the oil phase were greater than those in the aqueous phase of peppermint oil emulsions. The difference in the interfacial partition of resveratrol and proteins increased as the polyphenol solubility in bulk oil increased. Resveratrol solubility in the oil phase drove its transfer from the aqueous phase into the oil phase in all emulsions, except that the interfacial protein also contributed to the transfer in fish oil emulsions. The oil-water interface provided the microenvironment for the enrichment of resveratrol by proteins.

Digestion behavior, in vitro and in vivo bioavailability of cannabidiol in emulsions stabilized by whey protein-maltodextrin conjugate: Impact of carrier oil

An emulsion delivery system may be affected significantly by oil phase composition in terms of digestion behavior and bioavailability of the delivered substance. In this study, emulsions loaded with cannabidiol (CBD) were prepared with medium chain triglyceride (MCT), long chain triglyceride (LCT) or MCT/LCT(1:1) as carrier oil and whey protein-maltodextrin conjugate as emulsifier, and the digestion behavior of emulsion and bioavailability of CBD were assessed in vitro and in vivo. The particle size of emulsions throughout the in vitro digestion process was in the order of MCT < MCT/LCT < LCT, and three emulsions showed consistent particle size changes: stable in oral phase, sharply increased in gastric phase, and decreased in small intestine. After intestinal digestion, about 90% of free fatty acids (FFA) was released in MCT emulsion, followed by MCT/LCT (76%) and then LCT (45%). CBD was degraded during gastrointestinal digestion and the transformation stability of CBD in oil phase was in the order of LCT > MCT/LCT > MCT. Although CBD had higher bioaccessibility in MCT and MCT/LCT emulsions, the bioavailability of CBD in LCT was the highest (43%), followed by MCT/LCT (39%), MCT (33%). In vivo pharmacokinetic study showed that MCT/LCT and LCT were more favorable for CBD transport and absorption. The results may provide useful information for the construction of delivery systems, protecting CBD molecules, and improving their bioavailability.

Medium Chain Triglycerides Promote the Uptake of β-Carotene in O/W Emulsions via Intestinal Transporter SR-B1 in Caco-2 Cells.

This study aimed to elucidate the impacts of carrier oil types (long chain triglycerides (LCT), medium chain triglycerides (MCT), and orange oil (indigestible oil)) on the micellization and cellular uptake of β-carotene (BC) formulated in O/W emulsions, with an emphasis on the role of intestinal transporters. The micellization and cellular uptake of BC in the gastrointestinal tract were evaluated via an in vitro digestion model and a Caco-2 cell monolayer. And the interactions between lipids and intestinal transporters were monitored by nontargeted lipidomics, RT-PCR, and Western blot. The BC micellization rates followed a decreasing trend in emulsions: corn oil (69.47 ± 4.19%) > MCT (22.22 ± 0.89%) > orange oil (11.01 ± 2.86%), whereas the cellular uptake rate of BC was significantly higher in MCT emulsion (56.30 ± 20.13%) than in corn oil emulsion (14.01 ± 1.04%, p < 0.05). The knockdown of SR-B1 led to a 31.63% loss of BC cellular uptake from MCT micelles but had no effect on corn oil micelles. Lipidomics and transporter analysis revealed that TG (10:0/10:0/12:0) and TG (10:0/12:0/12:0) might be the fingerprint lipids that promoted the cellular absorption of BC-MCT micelles via stimulating the mRNA expression of SR-B1.

Premix Membrane Emulsification: Preparation and Stability of Medium-Chain Triglyceride Emulsions with Droplet Sizes below 100 nm.

Premix membrane emulsification is a promising method for the production of colloidal oil-in-water emulsions as drug carrier systems for intravenous administration. The present study investigated the possibility of preparing medium-chain triglyceride emulsions with a mean particle size below 100 nm and a narrow particle size distribution using sucrose laurate as an emulsifier. To manufacture the emulsions, a coarse pre-emulsion was repeatedly extruded through alumina membranes (Anodisc™) of 200 nm, 100 nm and 20 nm nominal pore size. When Anodisc™ membranes with 20 nm pore size were employed, nanoemulsions with z-average diameters of about 50 nm to 90 nm and polydispersity indices smaller than 0.08 could be obtained. Particle growth due to Ostwald ripening was observed over 18 weeks of storage. The Ostwald ripening rate linearly depended on the emulsifier concentration and the concentration of free emulsifier, indicating that micelles in the aqueous phase accelerated the Ostwald ripening process. Long-term stability of the nanoemulsions could be achieved by using a minimised emulsifier concentration or by osmotic stabilisation with soybean oil added in a mass ratio of 1:1 to the lipid phase.

The Feasibility and Tolerability of Medium Chain Triglycerides in Women with a Catamenial Seizure Pattern on the Modified Atkins Diet.

Ketogenic diet therapy (KDT), particularly modified Atkins diet (MAD), is increasingly recognized as a treatment for adults with epilepsy. Women with epilepsy (WWE) comprise 50% of people with epilepsy and approximately one in three have catamenial epilepsy. The purpose of this study was to determine whether adding a medium chain triglyceride emulsion to MAD to target catamenial seizures was feasible and well-tolerated. This was a prospective two-center study of pre-menopausal WWE with a catamenial seizure pattern on MAD. After a 1-month baseline interval with no changes in treatment, participants consumed betaquik® (Vitaflo International Ltd.) for 10 days each menstrual cycle starting 2 days prior to and encompassing the primary catamenial seizure pattern for five cycles. Participants recorded seizures, ketones, and menses, and completed surveys measuring tolerability. Sixteen women aged 20–50 years (mean 32) were enrolled and 13 (81.2%) completed the study. There was 100% adherence for consuming betaquik® in the women who completed the study and overall intervention adherence rate including the participants that dropped out was 81.2%. The most common side effects attributed to MAD alone prior to starting betaquik® were constipation and nausea, whereas abdominal pain, diarrhea, and nausea were reported after adding betaquik®. The high adherence rate and acceptable tolerability of betaquik® shows feasibility for future studies evaluating KDT-based treatments for catamenial seizures.

Blood clearance kinetics and organ delivery of medium-chain triglyceride and fish oil-containing lipid emulsions: Comparing different animal species

Medium-chain triglycerides (TG) (MCT) and fish oil (FO) TG are incorporated as the core TG component into intravenous (IV) lipid emulsions for infusion in parenteral nutrition. Bolus injections of IV emulsions, on the other hand, have emerged as a novel therapeutic approach to treat various acute disorders. However, intravascular metabolism and organ delivery of acute IV injection of emulsions containing both MCT and FO are not fully defined, nor have they been characterized across common experimental animal models. We characterized and compared blood clearance kinetics and organ distribution of bolus injections of MCT/FO emulsions among different animal species. We also examined whether sex differences or feeding status can affect catabolic properties of MCT/FO lipid emulsions. Blood clearance rates of lipid emulsions with specific TG composition were compared in rats IV injected with [3H]cholesteryl hexadecyl ether labeled pure n-6 long-chain (LCT) and n-3 FO TG lipid emulsions, or emulsions containing MCT and FO at different ratios (wt/wt), which include 8:2 (80% MCT: 20% FO), 5:4:1 (50% MCT: 40% LCT: 10% FO) and SMOF (30% LCT: 30% MCT: 25% olive oil: 10% FO). Dose-response effects (0.016mg-1.6mgTG/g body weight) of the MCT/FO 8:2 emulsions on blood clearance properties and organ delivery were determined in both mice and rats. Blood clearance kinetics and organ uptake of MCT/FO 8:2 emulsions were compared between male and female rats and between fed and fasted rats. Changes in plasma lipid profiles after acute injections of MCT/FO 8:2 lipid emulsion at different doses (0.043, 0.133, and 0.4mgTG/g body weight) were characterized in non-human primates (Cynomolgus monkeys). MCT/FO 8:2 emulsion was cleared faster in rats when compared with other emulsions with different TG contents. Mice had faster blood clearance and higher fractional catabolic rates (FCR) when compared with the rats injected with MCT/FO 8:2 emulsions regardless of the injected doses. Mice and rats had similar plasma TG and free fatty acid (FFA) levels after low- or high-dose injections of the MCT/FO emulsion. Tissue distribution of the MCT/FO 8:2 lipid emulsion are comparable between mice and rats, where liver had the highest uptake per recovered dose among all organs (>60%). Feeding status and sex differences did not alter the blood clearance rate of the MCT/FO 8:2 emulsion in rats. In a nonhuman primate model, dose-response increases in plasma TG and FFA were observed after IV injection of MCT/FO 8:2 emulsions within the 1st 10min. A lipid emulsion containing both MCT and FO TG is cleared rapidly in blood and readily available for organ uptake in rodent and primate animal models. Characterization of the blood clearance properties of the MCT/FO 8:2 emulsion administered in various animal models may provide further insight into the safety and efficacy profiles for future therapeutic use of bolus injections of MCT/FO emulsions in humans.

Impact of ripening inhibitors on molecular transport of antimicrobial components from essential oil nanoemulsions

The objective of this study was to provide insights into the mechanisms involved in the mass transport of antimicrobial compounds from essential oil nanoemulsions to bacterial cell membranes. Origanum oil-in-water nanoemulsions were produced using spontaneous emulsification by titrating a mixture of essential oil, ripening inhibitor, and surfactant (Tween 80) into 5 mM sodium citrate buffer (pH 3.5). Stable nanoemulsions containing relatively small droplets (d < 60 nm) were produced using this low-energy method. The nature of the ripening inhibitor used in the oil phase of the nanoemulsions affected the antimicrobial activity of the nanoemulsions: corn (LCT) > medium-chain triglycerides (MCT). Differences in antimicrobial activity were attributed to the differences in the rate of transfer of hydrophobic antimicrobial constituents from the nanoemulsion to the MCT emulsion, which was used to mimic the hydrophobic region of the bacterial cell membranes. Each antimicrobial nanoemulsion was separated from the MCT emulsion by a dialysis tubing. Dialysis tubing with two different pore sizes was used, one excluding nanoemulsion droplet and micelle delivery, allowing the delivery of antimicrobial compounds only through the aqueous phase and the other by both the aqueous phase and micelles. For origanum oil nanoemulsions, the delivery of all antimicrobial agents occurred more efficiently when micelles were present.

Stability and digestibility of one- or bi-layered medium-chain triglyceride emulsions with gum Arabic and whey protein isolates by pancreatic lipase in vitro.

Interfacial engineering approaches have been used to design functional foods so as to control lipase-induced digestion of emulsified lipids and release of bioactive lipophilic components in the gastrointestinal tract. In this study, emulsion droplets with the interface stabilized with gum Arabic (GA) and whey protein isolate (WPI) were prepared by mixing or sequential adsorption. WPI/GA intramolecular soluble complexes (ISCs) have superior emulsifying properties in stabilizing oil-in-water emulsions. The impact of the interfaces for WPI/GA ISC-layered (one-layered) and double-layered emulsions formed by sequential deposition of WPI or GA on the lipolysis of emulsions was investigated using an in vitro simulated gastrointestinal model. Transglutaminase and dithiothreitol were introduced to crosslink the interfacial proteins and improve the interfacial stability. The ISC-layered emulsion was less stable to aggregation than the double-layered ones in simulated gastric fluid due to dissociation of ISCs caused by the electrostatic screening of ions and proteolysis of interfacial proteins driven by pepsin. The ISC-layered emulsion conferred a significant slower rate and extent of lipid digestion compared to the double-layered emulsions post gastric proteolysis (P < 0.05). It is presumed for the ISC-layered emulsion that the destabilization to aggregation and coalescence within the simulated gastrointestinal fluids and the steric hindrance of the robust and thick interfacial layer might contribute to delaying free fatty acids release. It suggests that both the initial interfacial properties and the stability of the emulsified lipid droplets within the simulated gastrointestinal fluids play an important role in determining the rate and extent of lipid digestion. It is predicted that direct destabilization of emulsified lipids using interfacial engineering approaches has the potential of modifying lipid digestibility or bioactive release at specific sites within the gastrointestinal tract.

Ketogenic diet therapy for epilepsy during pregnancy: A case series

PurposeEvaluation of ketogenic diet (KD) therapies for seizure control during pregnancy when safety and appropriate management become considerations. Until now, no information has been available on seizure reduction and human pregnancy related outcomes in women treated with KD therapies. MethodWe describe two cases of pregnant women with epilepsy treated with KD therapy either as monotherapy (Case 1) or as adjunctive therapy (Case 2). ResultsCase 1: A 27 year old woman, gravida1, started the classic KD with medium chain triglyceride (MCT) emulsion and 75g carbohydrate-restriction, later reduced to 47g. Glucose levels were 4–6mmol/L and blood ketone levels ranged from 0.2 to 1.4mmol/L. Seizure frequency decreased and seizure-free days increased. Mild side effects included intolerance to MCT, reduced serum carnitine and vitamin levels, and mild hyperlipidemia. Fetal and neonatal growth was normal as was growth and development at 12 months.Case 2: A 36 year-old nulliparous woman was treated with a 20 gram carbohydrate-restricted Modified Atkins Diet (MAD) and lamotrigine, resulting in reduction of seizure frequency to once per month prior to pregnancy. Once pregnant, carbohydrates were increased to 30g. When seizures increased, lamotrigine dose was doubled. Urine ketones trended down during second trimester. A male was born with bilateral ear deformities of unknown significance. The child had a normal neurodevelopment at eight months. ConclusionNon-pharmacological epilepsy therapies like KD and MAD may be effective during human pregnancy. However, safety still has to be established. Further monitoring to identify potential long term side effects is warranted.

Influence of membrane material on the production of colloidal emulsions by premix membrane emulsification

Premix membrane emulsification is a possibility to produce colloidal emulsions as carrier systems for poorly water soluble drugs. During the extrusion of a coarse pre-emulsion through a porous membrane, the emulsion droplets are disrupted into smaller droplets. The influence of the membrane material on the emulsification success was investigated in dependence on the emulsifier. Premixed medium chain triglyceride (MCT) emulsions stabilized with five different emulsifiers were extruded through seven different hydrophilic polymeric membrane materials with pore sizes of 200nm. The resulting emulsions differed strongly in particle size and particle size distribution with a range of median particle sizes between 0.08μm and 11μm. The particle size of the emulsions did not depend mainly on the structure or thickness of the membrane but on the combination of emulsifier and membrane material. Contact angle measurements indicated that the wetting of the membrane with the continuous phase of the emulsion was decisive for achieving emulsions with colloidal particle sizes. The type of dispersed phase was of minor importance as basically the same results were obtained with peanut oil instead of MCT. To prove the assumption that only sufficiently hydrophilic membrane materials led to emulsions with colloidal particle sizes, two membrane materials were hydrophilized by plasma treatment. After hydrophilization, the emulsifying process led to emulsions with smaller particle sizes. The use of an alumina membrane (Anodisc®) improved the process even more. With this type of membrane, emulsions with a median particle size below 250nm and a narrow particle size distribution could be obtained with all investigated emulsifiers.

The emulsification properties of octenyl- and dodecenyl- succinylated inulins

The emulsification properties of a series of inulin samples modified using varying amounts of octenyl- and dodecenyl-succinic anhydride have been studied by determining the droplet size as a function of time, temperature and in the presence of electrolyte using laser diffraction. It was found that ∼2% modified inulin was required to stabilise 15% w/v medium chain triglyceride emulsions and that the minimum droplet size was achieved when the % hydrophobe content was >8 mol%. The dodecenyl derivatives produced emulsions with a smaller droplet size than the octenyl derivatives. Apart from OSA-inulin with a low degree of modification, stability was maintained when stored for a period of up to 21 days at room temperature and at 50 °C. The zeta potential of the emulsion droplets was determined by Laser Doppler Velocimetry and was found to increase from ∼5 mv to ∼60 mv as the pH increased from 2 to 7 due to the presence of carboxylate ions present in the linkage between the inulin and alkenyl chains. The droplet size was found to increase on the addition of electrolyte indicating that the adsorbed polymer layer was insufficient to provide a steric repulsive barrier and that stabilisation was mainly due to electrostatic repulsive forces.

Antimicrobial efficacy of an innovative emulsion of medium chain triglycerides against canine and feline periodontopathogens.

To test the in vitro antimicrobial efficacy of a non-toxic emulsion of free fatty acids against clinically relevant canine and feline periodontopathogens Antimicrobial kill kinetics were established utilising an alamarBlue(®) viability assay against 10 species of canine and feline periodontopathogens in the biofilm mode of growth at a concentration of 0·125% v/v medium chain triglyceride (ML:8) emulsion. The results were compared with 0·12% v/v chlorhexidine digluconate and a xylitol-containing dental formulation. Mammalian cellular cytotoxicity was also investigated for both the ML:8 emulsion and chlorhexidine digluconate (0·25 to 0·0625% v/v) using in vitro tissue culture techniques. No statistically significant difference was observed in the antimicrobial activity of the ML:8 emulsion and chlorhexidine digluconate; a high percentage kill rate (>70%) was achieved within 5 minutes of exposure and was maintained at subsequent time points. A statistically significant improvement in antibiofilm activity was observed with the ML:8 emulsion compared with the xylitol-containing formulation. The ML:8 emulsion possessed a significantly lower (P < 0·001) toxicity profile compared with the chlorhexidine digluconate in mammalian cellular cytotoxicity assays. The ML:8 emulsion exhibited significant potential as a putative effective antimicrobial alternative to chlorhexidine- and xylitol- based products for the reduction of canine and feline periodontopathogens.

Intralipid in lipophilic drug over dose: Dissecting fact from fiction.

Sir, We would like to share our views with regards to the case reported by Kute et al.,[1] and the comments made by Sanaei-Zadeh.[2] Intralipid emulsion (ILE) is an emerging and fascinating antidote against lipophilic drugs. Also, it is endorsed as an antidote in cardiac arrest secondary to local anesthetic agent and even in cases of intoxication with other lipophilic drugs when conventional resuscitative therapies have failed. Despite overwhelming growth of evidences for the use of ILE, many questions remain unanswered including the optimal dosage, formulation of lipid emulsion, patient safety aspects, and hazards of this agent. End-users shall remember that it is contraindicated in patients with known egg allergy, disorders of fat metabolism, liver disease, and acute myocardial infarction. In patients receiving total parenteral nutrition for an extended period of time, high triglycerides resulting from ILE infusion may alter immunity, lung function, and hemodynamics. With bolus dosing and at high doses as short-term rescue, ILE can theoretically result in hyperlipidemia, pulmonary injury, hepatosplenomegaly, thrombocytopenia, hyperlipidemia-induced pancreatitis, and fat embolism. Also, ILE lowers blood oxygen content, increases shunting, and causes pulmonary vasoconstriction. We, as yet do not know the acceptable upper limit of lipid infusion. Suggestions made from previous anecdotal experience may not be sufficient for all cases.[3] Standard long-chain triglyceride and mixtures of long and medium-chain triglyceride emulsions have both been used to reverse local anesthetic toxicity. Nevertheless, Ruan et al.,[4] had questioned the optimal formulation of lipid emulsion. We experienced reoccurrence of cardiotoxicity 50 min after administration of intralipid in a case of verapamil overdose which aroused the suspicion of rebound toxicity. Because of lipemia, it may be difficult to carry out laboratory studies or it may produce spurious results.[5] Clogging of lipid molecules in the dialysis filters was noticed after administration of ILE, despite using heparin to prime the system and/or epoprostenol infusion.[6] With the current gaps in our understanding, there is a need for more studies to explore the mechanisms and limitations of lipid in resuscitation, and to determine best practices and clinical guidelines before incorporating ILE in regular practice.[7] However, these guidelines require frequent debate, and revision based on upcoming experimental literature and clinical experience. Hence, it is suggested to undertake clinical trials with this agent.

Fat Overload Syndrome After the Rapid Infusion of SMOFlipid Emulsion

Fat overload syndrome is a well-known complication of intravenous lipid emulsion therapy. It is characterized by headaches, fever, jaundice, hepatosplenomegaly, respiratory distress, and spontaneous hemorrhage. Other symptoms include anemia, leukopenia, thrombocytopenia, low fibrinogen levels, and coagulopathy. Several reports in the literature describe fat overload syndrome caused by rapid infusion of lipid emulsions, all with soybean-based lipid emulsions. We report fat overload syndrome in a 2-year-old girl with short bowel syndrome on home parenteral nutrition. Fat overload syndrome occurred as a result of accidental, very rapid infusion of a 20% soy oil, medium-chain triglyceride, olive and fish oil-based lipid emulsion (SMOFlipid) that showed the same complications seen with an earlier lipid emulsion (Intralipid). The patient was successfully treated with supportive care combining fluid infusion, transfusion of platelets, and substitution of serum albumin (0.5 g/kg/d) and fresh-frozen plasma (10 mL/kg). In the next couple of days, she received extra platelets, erythrocyte transfusion, and filgrastim (Neupogen; 5 µg/kg/d) due to a very low leukocyte count. To the best of our knowledge, this is the first case of fat overload syndrome caused by SMOFlipid emulsion described in the literature.

Volatile Release from Self-Assembly Structured Emulsions: Effect of Monoglyceride Content, Oil Content, and Oil Type

Monoglycerides (MGs) can form self-assembled structures in emulsions, which can be used to control volatile release. In this study, initial headspace concentrations (C(initial)), maximum headspace concentrations (C(max)), release rates, and partition coefficients of propanol, diacetyl, hexanal, and limonene were determined in MG structured oil-in-water emulsions using dynamic and static headspace analyses. For all of the volatile compounds, C(initial) values above structured emulsions were significantly lower than those above unstructured emulsions and decreased with increasing MG contents (p < 0.05). However, volatiles had higher release rates in emulsions with higher MG contents. When oil content was reduced from 20 to 10%, C(initial) and C(max) increased for limonene and hexanal and decreased for propanol and diacetyl. When different oils were applied, both C(initial) and C(max) were significantly lower in medium-chain triglyceride emulsions than in soybean oil emulsions (p < 0.05). Static headspace analysis revealed that volatile compounds had significantly lower air-emulsion partition coefficients in the structured emulsions than in unstructured emulsions (p < 0.05). These results indicated that MG structured emulsions can be potentially used as delivery systems to modulate volatile release.

Short-term use of parenteral nutrition with a lipid emulsion containing a mixture of soybean oil, olive oil, medium-chain triglycerides, and fish oil: a randomized double-blind study in preterm infants.

Background: For premature neonates needing parenteral nutrition (PN), a balanced lipid supply is crucial. The authors hypothesized that a lipid emulsion containing medium-chain triglycerides (MCTs) and soybean, olive, and fish oils would be as safe and well tolerated as a soybean emulsion while beneficially influencing the fatty acid profile. Methods: Double-blind, controlled study in 53 neonates (<34 weeks’ gestation) randomized to receive at least 7 days of PN containing either an emulsion of MCTs and soybean, olive, and fish oils or a soybean oil emulsion. Target lipid dosage was 1.0 g fat/kg body weight [BW]/d on days 1–3, 2 g/kg BW/d on day 4, 3 g/kg BW/d on day 5, and 3.5 g/kg BW/d on days 6–14. Results: Test emulsion vs control, mean ± SD: baseline triglyceride concentrations were 0.52 ± 0.16 vs 0.54 ± 0.19 mmol/L and increased similarly in both groups to 0.69 ± 0.38 vs 0.67 ± 0.36 on day 8 of treatment (P = .781 for change). A significantly higher decrease in total and direct bilirubin vs baseline was seen in the test group compared with the control group P < .05 between groups). In plasma and red blood cell phospholipids, eicosapentaenoic acid and docosahexaenoic acid were higher, and the n-6/n-3 fatty acid ratio was lower in the test group (P < .05 vs control). Conclusions: The lipid emulsion, based on a mixture of MCTs and soybean, olive, and fish oils, was safe and well tolerated by preterm infants while beneficially modulating the fatty acid profile.

Lipid Resuscitation of Bupivacaine Toxicity

The superiority of Intralipid, a long-chain triglyceride (LCT) emulsion versus Lipovenoes, a long- and medium-chain triglyceride (LCT/MCT) emulsion, in reversing local anesthetic-induced cardiac arrest is poorly defined and needs to be determined. The study included two parts: in experiment A, bupivacaine (20 mg/kg) was injected to produce asystole. Either Intralipid 20% (LCT group, n = 30) or Lipovenoes 20% (LCT/MCT group, n = 30) with epinephrine was infused immediately. Return of spontaneous circulation and recurrence of asystole after resuscitation were recorded. In experiment B, 80 rats using the same model and resuscitation protocol were divided into 10 groups: LCT₀, LCT₁₅, LCT₃₀, LCT₆₀, and LCT₁₂₀ and LCT/MCT₀, LCT/MCT₁₅, LCT/MCT₃₀, LCT/MCT₆₀, and LCT/MCT₁₂₀ (n = 8 each; the subscripts represent respective observation period). LCT₁₅-LCT₁₂₀ and LCT/MCT₁₅-LCT/MCT₁₂₀ groups received Intralipid 20% or Lipovenoes 20%, respectively. Plasma and myocardial bupivacaine and triglyceride concentrations, as well as myocardial bioenergetics, were determined. In experiment A, 24 rats in LCT group and 23 in LCT/MCT group achieved return of spontaneous circulation (P = 0.754); among them, 2 (8.3%) and 8 (34.8%) rats suffered a repeated asystole, respectively (P = 0.027). In experiment B, plasma and myocardial bupivacaine concentrations in LCT₁₅ and LCT₆₀ groups were lower than LCT/MCT₁₅ and LCT/MCT₆₀ groups, respectively. Furthermore, the plasma bupivacaine level in LCT/MCT₆₀ group was higher than LCT/MCT₃₀ group (P = 0.003). LCT emulsion may be superior to LCT/MCT emulsion in treating bupivacaine-related cardiotoxicity as it was associated with fewer recurrences of asystole after resuscitation and lower myocardial bupivacaine concentrations.

Immunomodulatory and physical effects of oil composition in vaccine adjuvant emulsions

Squalene-based oil-in-water emulsions have been used for years in some seasonal and pandemic influenza vaccines. However, concerns have been expressed regarding squalene source and potential biological activities. Little information is available regarding the immunomodulatory activity of squalene in comparison with other metabolizable oils in the context of oil-in-water emulsions formulated with vaccines. The present work describes the manufacture and physical characterization of emulsions composed of different classes of oils, including squalene, long chain triglycerides, a medium chain triglyceride, and a perfluorocarbon, all emulsified with egg phosphatidylcholine. Some differences were apparent among the non-squalene oils in terms of emulsion stability, including higher size polydispersity in the perfluorocarbon emulsion, more rapid visual instability at 60°C for the long-chain triglyceride and perfluorocarbon emulsions, and an increased creaming rate in the medium-chain triglyceride emulsion at 60°C as detected by laser scattering optical profiling. The biological activity of each of these emulsions was compared when formulated with either a recombinant malaria antigen or a split-virus inactivated influenza vaccine. Overall, vaccines containing the squalene emulsion elicited higher antibody titers and more abundant long-lived plasma cells than vaccines containing emulsions based on other oils. Since squalene-based emulsions show higher adjuvant potency compared to the other oils tested, non-squalene oils may be more suitable as carriers of amphiphilic or hydrophobic immunostimulatory molecules (such as TLR agonists) rather than as stand-alone adjuvants.