Emulsion lipid

Multivesicular Liposomes Kim and his colleages described a method for the preparation of cell size liposomes with high encapsulation efficiency the so-called multivesicular liposomes (Kim et al., 1983). The lipid phase consists of a combination of amphiphatic lipids and a small amount of triglycerides (triolein or trioctanoin) dissolved in chloroform-diethyl ether (1 1). The aqueous phase is slowly added to the organic phase and after vigorous shaking a water-ip-lipid emulsion is formed (Fig. 2A-B). Via a narrow Pasteur pipet the emulsion is subsequently added to a sucrose solution. 

Absorption kinetic studies on fasted rats dosed by lipid-emulsion gavage revealed rapid appearance of triehloroethylene in the blood (typieally peaking at 15 minutes post-exposure) followed by rapid disappearance (Templin et al. 1993). Rats similarly dosed with radiolabelled trichloroethylene showed rapid serum albumin adduction which peaked at 4-8 hours, then decayed with a half-life consistent with that of albumin itself (Stevens et al. 1992). However, some of the detected radioactivity may have been due to trichloroethylene metabolites rather than the parent compound. 

With few exceptions, small particles of vegetable foods are generally stripped of their more accessible nutrients during digestion in the GI tract. In this way starch, protein, fat and water-soluble small components (sugars, minerals) are usually well absorbed. This is not always the case, however, for larger food particles or for molecules that cannot diffuse out of the celF tissue. Neither is it the case for the lipid-soluble components. These need to be dissolved in lipid before they can be physically removed from the cell to the absorptive surface, since the cell wall is unlikely to be permeable to lipid emulsions or micelles, and the presence of lipases will strip away the solvating lipid. 

Research of the pharmacokinetic parameters of lipid emulsion of paclitaxel 91... 

Intravenous lipid emulsions are used as an energy source in PN and to prevent or treat essential fatty acid deficiency. 

PN admixtures can be prepared by mixing all components into one bag [3-in-l admixture or a total nutrient admixture (TNA)] or by mixing and infusing dextrose, amino acids, and all other components together and infusing intravenous lipid emulsion separately (2-and-l admixture). 

PN should provide a balanced nutritional intake, including macronutrients, micronutrients, and fluid. Macronutrients, including amino acids, dextrose, and intravenous lipid emulsions, are important sources of structural and energy-yielding substrates. A balanced PN formulation includes 10% to 20% of total daily calories from amino acids, 50% to 60% of total daily calories from dextrose, and 20% to 30% of total daily calories from intravenous lipid emulsion. Micronutrients, including electrolytes, vitamins, and trace elements, are required to support essential biochemical reactions. Parenteral... 

Intravenous lipid emulsions differ in their concentration (10%, 20%, and 30%), caloric density, natural source of lipids, and ratio of phospholipids to triglycerides (PL TG). Table 97-2 shows a comparison of commercially available intravenous lipid emulsions in the United States. The 10%, 20%, and 30% lipid emulsions provide 1.1 kcal/mL (4.6 kJ/mL), 2 kcal/mL (8.4 kJ/mL), and 3 kcal/mL (12.6 kJ/mL) with a PL TG of 0.12, 0.06 and 0.04 respectively. The lower PL TG indicates a lower phospholipid content and translates to abetter clearance of the 20% and 30% lipid emulsions compared with the 10% lipid emulsion.9 The 30% lipid emulsion is only approved for infusion in a TNA and should not be infused directly into patients. 

Intravenous lipid emulsion particles are hydrolyzed in the bloodstream by the enzyme lipoprotein lipase to release free fatty acids and glycerol. Free fatty acids then are be taken up into adipose tissue for storage (triglycerides), oxidized to energy in various tissues (e.g., skeletal muscle), or recycled in the liver to make lipoproteins. 

The essential fatty acids in humans are linoleic acid (C-18 2 N-6) and a-linolenic acid (C18 3 N-3). Arachidonic acid (C20 4 N-6) is also essential but can be synthesized from linoleic acid. Administration of 2% to 4% of total daily calories as linoleic acid should be adequate to prevent essential fatty acid deficiency in adults (e.g., infusion of 500 mL of 20% intravenous lipid emulsion once weekly).7 Biochemical evidence of essential fatty acid deficiency can develop in about 2 to 4 weeks in adult patients receiving lipid-free PN, and clinical manifestations generally appear after an additional... 

Intravenous lipid emulsions are also a source of calories. The typical daily dose in adults is approximately 0.5 to 1 g/kg per day. In the absence of hypertriglyceridemia, substituting a portion of dextrose calories with lipid calories may be beneficial in situations where dextrose infusion may lead to complications (e.g., hyperglycemia). Some examples include patients with diabetes mellitus or pancreatic disease and patients under severe stress (e.g., trauma or burns) who are at risk for hyperglycemia. The maximum of dose of lipid emulsions is 2.5 g/kg per day,7 or 60% of total daily calories, although doses this high are used rarely in practice. 

Order of mixing. Calcium and phosphate should be separated when mixing PN admixtures (e.g., add phosphate first, then all other PN components, and then add calcium last) if calcium is added before all other components are in the bag, including lipid emulsion, then the volume in the bag at the time calcium is added must be used to determine the maximum calcium that can be added. 

The benefit and necessity of adding heparin to PN are unclear. There are also concerns about the stability/compatibility of intravenous lipid emulsions with heparin added at concentrations above 1 unit/mL. Heparin should be omitted in patients with active bleeding, thrombocytopenia, heparin-induced thrombocytopenia (HIT), or heparin allergy. 

Iron-deficiency anemia in chronic PN patients may be due to underlying clinical conditions and the lack of iron supplementation in PN. Parenteral iron therapy becomes necessary in iron-deficient patients who cannot absorb or tolerate oral iron. Parenteral iron should be used with caution owing to infusion-related adverse effects. A test dose of 25 mg of iron dextran should be administered first, and the patient should be monitored for adverse effects for at least 60 minutes. Intravenous iron dextran then may be added to lipid-free PN at a daily dose of 100 mg until the total iron dose is given. Iron dextran is not compatible with intravenous lipid emulsions at therapeutic doses and can cause oiling out of the emulsion. Other parenteral iron formulations (e.g., iron sucrose and ferric gluconate) have not been evaluated for compounding in PN and should not be added to PN formulations. 

PPN admixtures should be coinfused with intravenous lipid emulsion when using the 2-and-l PN because this may decrease the risk of phlebitis. Infectious and mechanical complications may be lower with PPN compared with central venous PN administration. However, because of the risk of phlebitis and osmolarity limit, PPN admixtures have low macronutrient concentrations and therefore require large fluid volumes to meet a patient s nutritional requirements. Given these limitations, every effort should be made to obtain central venous... 

Advantages Simplified regimen for patient Increased patient compliance at home Decreased labor Decreased costs Decreased risk of contamination (due to less manipulation) Minimize infusion-related reactions from intravenous lipid emulsions Decreased vein irritation (especially with PPN) Improved stability compared to TNA Increased number of compatible medications Decreased bacterial growth compared to TNA Easier visual inspection Can use 0.22-micron bacterial retention filter Cost savings if unused (i.e. not spiked) intravenous lipid emulsion can be reused... 

Disadvantages Decreased stability compared to 2-in-1 PN Cannot use 0.22-micron bacterial retention filter Increased bacterial growth compared to 2-in-1 PN Visual inspection is difficult Limited compatibility with medications Increased labor and costs (if intravenous lipid emulsion infused separately) Increased vein irritation, especially if PPN is not coinfused with intravenous lipid emulsion... 

Another concern is the coinfusion of intravenous medications with PN admixtures. Many intravenous medications have limited compatibility with 3-in-l formulations but may be coinfused with a 2-and-l formulation.23,24 Some medications can be coinfused at the Y-site, few medications can be mixed directly into the PN solution or coinfused with intravenous lipid emulsion, and some cannot be mixed or coinfused with the PN admixture.23,24 Always consult compatibility data before adding a medication to a PN admixture or coinfusing with PN. Medications that are compatible should be added to PN only if it is reasonable and safe (i.e., based on toxicity profile, pharma-cokinetic/pharmacodynamic considerations). 

Intravenous lipid emulsion Typical intravenous lipid emulsion should provide -20-30% of total daily calories Can be an alternative source of calories in patients with diabetes or hyperglycemia—consider increasing calories from intravenous lipid emulsion in these patients (e.g., 30% of total daily calories) Total daily goal calories = 1 800 kcal/day I 800 kcal/day x 0.3 = 540 kcal/day 540 kcal/day to be provided from intravenous lipid emulsion kcaPmL3 mL 20°/° intravenous lipid emulsion/day (11.25 mL/hour x 24 hours, so round to 11 mL/hour) II mL/hour x 24 hours = 264 mL/day of 20% intravenous lipid emulsion = 528 kcal/day... 

Dextrose Dextrose infusion rate should be -3 1 mg/kg per minute, should comprise -50-60% of total daily calories Since this patient has type 2 diabetes mellitus, consider a goal of -3 mg/kg per minute Provide remainder of total daily calories as dextrose Total daily goal calories = 1 800 kcal/day 1 800 kcal/day -528 kcal/day (from intravenous lipid emulsion) 1272 kcal/day -440 kcal/day (from amino acids) 832 kcal/day to make up with dextrose. 3.4 kcal/g Y 245 8 dextrose/daY If using a 70% stock dextrose solution 245 g x 100 mL. 70 g 245 g/day x 3.4 kcal/g = 833 kcal/day As a double-check, convert to mg/kg/minute 245 g dextrose/day x 1000 mg/1 g x 1 day/1440 minute = 1 70.1 mg/minute 170.1 mg/minute -2.8 mg/kg per minute... 

A higher PL TG ratio in the 10% lipid emulsion has been proposed to cause the appearance of the abnormal lipoprotein X particles [rich in phospholipids (-60%) and cholesterol (-25%), small amounts of triglycerides] in the blood.9,35 Lipoprotein X... 

Coalescence Fusion of smaller lipid emulsion particles forming larger particles, resulting in destabilization of the emulsion. 

Creaming Aggregation of lipid emulsion particles that then migrate to the surface of the emulsion that can be reversed with mild agitation. 

Lipoprotein lipase Enzyme located in the capillary endothelium involved in the breakdown of intravenous lipid emulsion particles. 

Oiling out Continued coalescence of lipid emulsion particles, resulting in irreversible separation of the emulsion (or breaking of the emulsion). 

---