Clinical use of liposome technology for the delivery of nutrients to patients with the short bowel syndrome

Short bowel syndrome may result from extensive resection of the small bowel. Because the transport of bile salts, cobalamin (vitamin B 12 ), and cholesterol is localized to the ileum, resection of this region is poorly tolerated. Patients who have had their ileum resected cannot absorb cholesterol, long chain fatty acids, fat soluble vitamins (A, D, E, and K), cobalamin (vitamin B 12 ), and the metal ions (Ca 2&plus; , Mg 2&plus; , and Zn 2&plus; ). Liposomes are suitable biological vehicles for the non-parenteral delivery of these fat and water soluble nutrients directly into the blood of patients with the small bowel syndrome. Liposomes are compartmentalized vesicles consisting of bilayer lipids enclosing aqueous chambers. The lipid and water soluble nutrients can be commercially packaged in their respective compartments and delivered directly into the blood stream of these patients, thereby bypassing the intestines. The liposomes can pass through water barriers. Their solubility in lipid rich surface membranes permits the release of the enclosed nutrients and their diffusion into the interior of cells.

DETAILED DESCRIPTION OF THE INVENTION The biochemical structure of liposomes make them excellent non-parenteral vehicles for the delivery of those fat and water soluble nutrients that cannot be absorbed in the intestines of patients who have had their ileum resected. In addition, the physical properties of the nutrients that cannot be absorbed allow them to be commercially incorporated into liposomes. Lipids are small-water-insoluble biomolecules generally containing fatty acids, sterols, or isoprenoid compounds. Lipids are soluble in nonpolar solvents. Lipids cannot enter into the blood stream unpackaged because they would coalesce, impeding the flow of blood. Lipids must be packaged in a form that is soluble in blood. The commercial incorporation of the fat soluble nutrients, cholesterol, long chain fatty acids, and the fat soluble vitamins (A, D, E, and K) would simulate the physiological packaging of these same nutrients into chylomicrons by intestinal epithelial cells for their transport into the blood to tissues 4-5 . Liposomes and chylomicrons are similar in that they are soluble in the blood and can transport lipids to tissues 5-7 . Liposomes differ from chylomicrons in that they consist of a bilayer lipid membrane. Chylomicrons consist of a monolayer membrane of phospholipids. Liposomes also differ from chylomicrons in that they can transport both fat and water soluble nutrients. Cholesterol, long chain fatty acids, and fat soluble vitamins require micellar formation before they can enter into the intestinal epithelial cells. A certain concentration of bile salts are required for micellar formation of these lipids 4 . Patients who have had their ileum resected cannot absorb long chain fatty acids, cholesterol, and fat soluble vitamins because they lack bile salts 1-3 . Their bile salts are not reabsorbed, but excreted. Consequently, the dietary intake of these nutrients are not absorbed in the small bowel, but are excreted. Because of the physical characteristics of these fat soluble nutrients, they can be commercially packaged in liposomes and delivered directly into the blood of patients with the short bowel syndrome. Liposome technology has been perfected 5-7 . Liposomes have numerous uses as biochemical and biophysical tools. Liposomes are used as vehicles for the delivery of both water and oil soluble materials into cells 5-7 . Liposome technology is based on the amphipathic characteristics of certain classes of lipids, especially the phosholipids 5-8 . Phospholipids form bilayer lipids that are similar to the membranes of human cells. Amphiphatic lipids contain both polar and nonpolar regions 5-8 . Phospholipids are composed of a hydrophobic (nonpolar) “tail” region, usually derived from long chain fatty acids, and a hydrophillic (polar) “head” region which contains a phosphate group with a negative charge, and in some instances a group with a positive charge 5-8 . The difference in the regions at the two ends of phospholipid molecules causes them to concentrate at interfaces between aqueous and non-aqueous phases within the cell. Their hydrophobic regions react with the lipids and their hydrophillic regions react with water. Membranes naturally tend to form closed structures, to avoid exposing the hydrophobic ends of lipid bilayers to the solvent. Liposomes can be made with membrane fragments or synthetic phospholipids 5-7 . They can be made to contain compounds buried in the membrane or totally enclosed 5-7 . Membrane bound components can be used to target the liposomes to the appropriate cells and fusion with the cell membranes delivers the contents of the liposome to the interior of cells. When amphipathic lipids are mixed with water they form microscopic lipid aggregates in a phase separate from their aqueous surroundings 5-7 . The lipid molecules cluster together with their hydrophobic moieties in contact with each other and their hydrophillic groups interacting with the water. The hydrophobic interactions among lipid molecules provide the thermodynamic driving force for the formation and maintenance of these structures 5-6 . There are three types of lipid aggregates formed when amphipathic lipids are mixed with water (1) spherical micelles (2) a bilayer and (3) a liposome. In the micelles, the hydrophobic chains of the fatty acids are sequestered in the core of the sphere 5-6 . There is virtually no water in the interior of a micelle 6 . In a bilayer, all acyl side chains except those at the edges of the sheet are protected from the interaction with water 5-6 . When an extensive two-dimensional bilayer folds on itself, it forms a liposome, a three dimensional hollow vesicle enclosing an aqueous cavity. 5-7 By forming vesicles, bilayer sheets lose their hydrophobic edge regions, thereby achieving maximal stability in their aqueous environment These bilayer vesicles enclose water, creating a separate aqueous compartment. Liposomes are also known as lipid vesicles. The membranes enclose a portion of the aqueous phase much like the cell membrane which encloses the cell 5-8 . A widely used synthetic phospholipid for the commercial production of liposomes is phosphatidylcholine (lecithin) 5-7 . Phosphatidylcholine is an amphipathic phosphoacylglycerol 4-8 . It consists of an elongated nonpolar (hydrophobic “tail”), the two long fatty acyl chains and a polar (hydrophillic “head”) group. The two fatty acid molecules are esterfied to two hydroxy groups of glycerol, and a second alcohol, the head group, esterfied to the third hydroxyl of glycerol via a phosphodiester bond. When phospholipids are dispersed in water, they spontaneously form bilayer membranes. These bilayer membranes are also called lamellae. They are composed of two monolayer sheets of lipid molecules with their nonpolar (hydrophobic) surfaces facing each other and their polar (hydrophillic) surfaces facing the aqueous medium. Thus, the basic foundation of the liposome is a lipid bilayer 5-7 . In such a layer, the nonpolar hydrophobic tails of the phospholipid molecules point inward, forming a nonpolar zone in the interior of the bilayer 5-7 . The nonpolar zone surrounds the innermost aqueous (hydrophillic) compartment of the liposome 5-7 . The simplest laboratory procedure for the formation of liposomes is the hand shaking of an aqueous solution of anhydrous lipids with water for seconds to hours, depending on the natures of the lipids or aqueous phases 5-7 . This simple procedure spontaneously yields large, multi-lamellar liposomes with diameter 1 to 10 micrometers, which are composed of a few to hundreds of concentric lipid bilayers alternating with layers of aqueous phases 5-7 . Smaller unilamellar vesicles of 20 nanometer in diameter can be produced by subjecting multilamellar vesicles to high-frequency ultrasound waves 6,7 . The sonicated mixture results in a dispersion of closed vesicles that are uniform in size. Vesicles can also be prepared by rapidly mixing a solution of lipid in ethanol with water 6 . This is usually done by injecting the lipid through a fine needle into an aqueous solution 6 . Vesicles formed by these methods are nearly spherical in shape and have a diameter about 500 angstrom units. Larger vesicle of 1 &mgr;m, in diameter can be prepared by slowly evaporating the organic solvent from a suspension of phospholipid in a mixed solvent system 5-7 . Fusion of small unilamellar vesicles by methods requiring particular lipids or stringent dehydration-hydration conditions can yield unilamellar vesicles as large or larger than cells 5-7 . Ions or molecules can be trapped in the aqueous compartments of lipid vesicles (liposomes) by forming them in the presence of those water soluble substances desired to be delivered into other cells 5-7 . The vesicles can be loaded almost with any water-soluble molecule 5-7 . Liposome technology has advanced above and beyond the production of the conventional liposome 9,10,11 . The development of multivesicular lipid-based carrier technology provides for sustained and controlled delivery of therapeutic agents 9,10,11 . Also, the multivesicular technology permits high drug loading and the modulation of drug release rates 12 . The biocompatibility of the liposome matrix allows for its delivery into sensitive areas of the body without a “foreign body response. 9,10,11 ” Current multivesicular liposome formulations have been shown to exhibit excellent storage stability 9,10,11,12 . The multivesicular liposomes have been shown to be cost effective because they can be readily manufactured on a commercial scale 13 . Liposomes appear to be the ideal biological vehicles for the delivery of fat and water soluble nutrients to patients with the short bowel syndrome who do not require parenteral nutrition. Most of the nutrients that are malabsorbed in these patients are processed and /or stored in the liver. It was previously mentioned that a major advantage of using liposomes for the delivery of those nutrients that cannot be absorbed by patients with the short bowel syndrome is that they accumulate in the liver, where they are usually stored and metabolized. It was also mentioned earlier that fat and water soluble nutrients can be commercially packaged together in liposomes and delivered simultaneously into the blood stream of patients with the small bowel syndrome. The Rationale for the Delivery of Cholesterol via Liposomes to Patients with the Short Bowel Syndrome: Although cholesterol is an essential molecule in humans, it is not required in the diet 4 . It can be synthesized in the liver from the simple precursor, acetyl Coenzyme A 4 . However, patients with short bowel syndrome tend to have below normal cholesterol levels for several reasons. A major reason why patients with the short bowel syndrome have low blood cholesterol levels is due to its malabsorption. Bile salts are absorbed from the ileum together with dietary cholesterol 4 . They enter the portal circulation, which carries them to the liver, where they can be re-excreted into the duodenum (upper portion of the small bowel) 4 . Cholesterol requires micellar solubilization by the bile salts for absorption 4 . Bile salts are not reabsorbed in individuals who have had their ileum resected 1-3 . Therefore, they cannot absorb dietary cholesterol 4 . The dietary cholesterol is lost in the feces. Another reason why patients with the short bowel syndrome have low blood cholesterol levels is because of the increased demand on the intra-hepatic cholesterol pool for the biosynthesis of bile salts 4 . Bile salts are synthesized in the liver from cholesterol. According to the literature, a critical concentration of bile salts for micelle formation (5 to 10 &mgr;mmol per milliliter) is maintained by a very efficient enterohepatic circulation of bile salts 4 . It was stated in the literature that the total bile salt pool is about 2 to 4 grams and that about 95% of it is actively reabsorbed in the ileum and returned to the liver by the venous portal system 4 . It was further stated in the literature that approximately, 20 to 30 grams of bile salts recirculate in the enterohepatic circulation 3 . It was also reported in the literature that only about 200 to 600 milligrams of bile salts are excreted in the feces per day 3 . According to the literature, the amount of bile salts that is excreted into the feces daily must be replaced by the hepatic biosynthesis of cholesterol 3,4 . The amount of bile salts excreted is much larger in patients with the short bowel syndrome. Since the bile salts have to be replaced by hepatic cholesterol, much of the cholesterol synthesized in the liver is utilized in the biosynthesis of bile salts. Therefore, increased synthesis of bile salts by the liver results in low blood levels of cholesterol in patients who have had their ileum resected. The diarrhea that results from intestinal resection may be on the basis of the region removed, for example, the ileum with its special transport sites for active bile salt absorption or the length of the bowel resected. At least 50% of the small bowel is required in order to avoid diarrhea and malnutrition associated with the small bowel syndromes. The diarrhea in patients with the short bowel syndrome results from the excretory effects of malabsorbed bile salts on the colonic mucosa 1-3 . The bile salts are irritants to the colonic mucosa 2-3 . Cholestyramine is the treatment of choice for the diarrhea in patients with the short bowel syndrome. Cholestyramine also causes a reduction in the serum cholesterol 4 . Cholestyramine binds bile salts and prevents their reabsorption 4 . The binding of the bile salts by cholestyramine leads to the increased conversion of cholesterol to bile salts 4 . This results in a further diminished cholesterol intrahepatic pool. In addition, bile salts are necessary for the absorption of cholesterol from the small bowel; hence there is also decreased absorption of cholesterol. Cholesterol is a membrane constituent 4 . Cholesterol adds stability to the phospholipid bilayer of membranes 4 . All growing animal tissues need cholesterol for membrane synthesis, and some organs (adrenal gland and gonads), for example, use cholesterol as a precursor for steroid hormone production 4-6 . Cholesterol is a precursor of vitamin D 4-6 . All steroid hormones are derived from cholesterol 4-6 . Two classes of steroid hormones are synthesized in the cortex of the adrenal gland: mineralcorticoids which control the reabsorption of inorganic ions (Na &plus; , Cl − , and HC0 3 −) by the kidney, and glucorticoids, which regulate gluconeogenesis and also reduce the inflammatory response. As previously mentioned, cholesterol serves as the precursor of bile salts, detergent-like compounds that function in the process of lipid digestion and absorption 4 . Cholesterol is the precursor of all sex hormones 4-6 . The sex hormones are produced in the male and female gonads and the placenta. They include androgens (e.g., testosterone and estrogens (e,g., estradiol) which influence the development of secondary sexual characteristics in males and females, respectively, and progesterone, which regulates the reproductive cycle in females. The low blood cholesterol levels in individuals with the small bowel syndrome must be replenished periodically with exogenous cholesterol, especially in those who are being treated with cholestyramine for the diarrhea. The additive effect of cholestyramine on an already diminished intrahepatic cholesterol pool can profoundly affect the health and well being of patients with the short bowel syndrome. Therefore, it is absolutely necessary that patients with the small bowel syndrome receive exogenous cholesterol replacement therapy, if required. Extemely low blood levels of cholesterol could adversely affect growth and reproductive maturity in pediatric patients with the small bowel syndrome. Cholesterol is amphipathic 5-6 . It has a hydrophobic and a hydrophillic unit. It has a polar head group, the hydroxyl group at C-3 and a nonpolar hydrocarbon body (the steroid nucleus and the hydrocarbon side-chain at C-17) 6 . Cholesterol in its extended form is about as long as 16-carbon fatty acid 6 . According to the literature, free cholesterol inserts into bilayers with its long axis perpendicular to the plane of the membrane 6 . The hydroxyl group of cholesterol hydrogen bonds to a carbonyl oxygen atom of a phospholipid head group , whereas the hydrocarbon tail of cholesterol is located in the nonpolar core of the bilayer 6 . In cholesterol esters, the hydroxyl group is esterfied to a fatty acid. Chylomicrons transport both free cholesterol and cholesterol esters 4 . It was stated in the literature that the esterfication of cholesterol causes the molecule to become more hydrophobic. It was further stated in the literature that cholesterol esters are more readily packaged in lipoprotein particles, or lipid droplets in the cytosol of the cell. According to the literature, the bulk of cholesterol is transported in the form of cholesterol esters in chylomicrons and lipoproteins. The incorporation of cholesterol as esters into liposomes would simulate the physiological packaging and transport of cholesterol by chylomicrons. If cholesterol esters are commercially incorporated into liposomes, they would be sequestered into the hydrophobic interior of the structures. Rationale for the Delivery of the Essential Long Chain Fatty Acids via Liposomes into the Blood of Patients with the Short Bowel Syndrome: Fatty acids are derived from the diet or synthesized mainly in the liver from glucose. The fatty acids are divided into four groups: short chains with 2 or 3 carbons, medium chains with 4-12 carbons, long chains with 21-20 carbons, and very long chains with more than 20 carbons. Long chain fatty acids with 14-20 carbons predominate in the body. It was previously mentioned that long chain fatty acids cannot be absorbed by patients who have had their ileum resected because they require micellar solubilization. These patients lack the necessary bile salts for micellar solubilization of long chain fatty acids. Consequently, they are not absorbed from their diets. They are excreted and contribute significantly to the steatorrhea characteristic of the short bowel syndrome. The body cannot synthesize the two essential long chain fatty acids, linoleate and linolenate 5-6 . Because these two long chain fatty acids are necessary precursors for the synthesis of other products , they are essential fatty acids for humans. They must be obtained from plant material in the diet. Once ingested linoleate may be converted into certain other polyunsaturated fatty acids, particularly &ggr;-linolenate, eicosatetraenoate (arachidonate) which can only be made from linoleate 4-6 . Arachidonate, 20: 4 (&Dgr; 5,8,11,14 ), is an essential precursor of regulatory lipids, the eicosanoids. The prostaglandins, thromboxanes, and leukotrienes belong to this group of compounds. The eicosanoids are a family of very potent biological signaling molecules that act as short-range messengers affecting tissues near the cells that produce them 4-5 . This family of compounds are known to be involved in reproductive functions; in the inflammation, fever, and pain associated with injury or disease; in the formation of blood clots and the regulation of blood pressure; in gastric acid secretion; and in a variety of other processes important in human health and disease. Therefore, it is absolutely necessary that individuals who have had their ileum resected receive these two essential fatty acids. Fatty acids are carboxylic acids with hydrocarbon chains of 4 to 36 carbons 5 . In some fatty acids, the chain is fully saturated (contains no double bonds). The physical properties of fatty acids, and of compounds that contain them, are largely determined by the length and degree of unsaturation of the hydrocarbon chain 5 . The nonpolar hydrocarbon chain accounts for the poor solubility of fatty acids in water. The longer the fatty acyl chain and the fewer the double bonds, the lower the solubility in water 5 . The carboxylic acid group is polar (and ionized at neutral pH), and account for the slight solubility of short-chain fatty acids in water 5 . In vertebrate animals, free fatty acids (having a free carboxylate group) circulate in the blood bound to a protein carrier, serum albumin 5 . However, fatty acids are present mostly as carboxylic acid derivatives such as esters or amides 5 . In general, fatty acids that lack the charged carboxylate group are less soluble in water than are the free charged carboxylic acids 5 . The long chain fatty acids are essentially hydrophobic and require solubilization by bile salts before they can be absorbed 5 . The two long chain fatty acids, linoleic and linolenate can be incorporated into liposomes as ionized or esterified molecules. In either form, they would most likely occupy the hydrophobic interior of the liposome because of their poor solubility in water. Even if they were incorporated into liposomes in the ionized form, the double bonds associated with both essential fatty acids would not be enough to offset the strong hydrophobicity of the long hydrocarbon chains, (“tails” of 18 carbon atoms). Perhaps, the possibility exists that the essential long chain fatty acids could be esterfied with cholesterol under laboratory conditions and incorporated into liposomes. Cholesterol contains 27 carbon atoms. It has 8 carbon atoms in its branched aliphatic side chain, and its steroid nucleus contains a double bond between carbons 5 and 6 and a hydroxyl group at position 3 . The 3-OH group of cholesterol allows it to react with fatty acids. This hydroxy group can be esterfied to fatty acids, producing cholesterol esters. An ester linkage is formed when a carboxylic acid and an alcohol react, splitting out water 4 . In human liver cells, cholesterol esters are formed through the action of acyl-:cholesterol acyltransferase (ACAT). This enzyme is also located in cells, particularly, those needed to store cholesterol for the synthesis of steroid hormones 4 . The synthesis of cholesterol esters converts cholesterol into an even more hydrophobic form for storage and transport. Cholesterol esters occupy the hydrophobic interior of chylonicrons. If the essential long chain fatty acids are esterfied with cholesterol and incorporated into liposomes, they also would be sequestered into the hydrophobic interior of the structure. Cholesterol esters are transported to other tissues that use cholesterol, for example, the gonads for the synthesis of steroid hormones, or are stored in the liver 4 . The cholesterol esters can be hydrolyzed by liver endosomal enzymes into free cholesterol and fatty acids 4 . The long chain fatty acids require the action of bile salts before they are packaged as triacyglycerols and incorporated into chylomicrons by intestinal epithelial cells. Triacyglycerols are fatty acid esters of glycerol. Triacylglycerols contain three fatty acid molecules esterfied to the three hydroxyl groups of glycerol. The triacylglycerols are primarily storage fats. The insertion of the long chain fatty acids as triacylglycerols into liposomes would simulate the normal intestinal packaging of them into chylomicrons. Because of the polar hydroxyls of glycerol and the polar carboxylates of the fatty acids are bound in ester linkages, triacylglycerols are nonpolar, hydrophobic molecules, essentially insoluble in water 5 . If the long chain fatty acids (linoleate and linolenate) are incorporated as triacylglycerols into liposomes, they would also be sequestered into the hydrophobic interior of the structures. Thus, their incorporation into liposomes as triacylglycerols simulate the packaging of those into chylomicrons by the intestinal epithelial cells. Large amounts of triacylglycerols are stored in human cells called adipocytes, or fat cells. Many patients with the small bowel syndrome are underweight. The incorporation of long chain fatty acids as triacylglycerols into the liposomes could enable them to achieve an ideal body weight commensurate with their height and body frame. The fat soluble vitamins A, D, E, and K are isoprenoid compounds 5 . Vitamin A is a pigment essential to vision. A deficiency in vitamin A may lead to night blindness. Vitamin D is a derivative of cholesterol and the precursor hormone essential in calcium and phosphate metabolism in vertebrate animals. A deficiency in vitamin D leads to defective bone formation resulting in rickets. Vitamin K is a lipid cofactor required for normal blood clotting. Vitamin K deficiency can result in defective coagulation. Vitamin E is the collective name for a group of closely related lipids called tocopherols, all of which contain a substituted aromatic ring and a long carbon side chain 5 . Vitamin E deficiencies can lead to a scaly skin disorder, muscular weakness and wasting, and sterility. Vitamin E deficiencies can cause serious neurological abnormalities. Also tocopherols react with and destroy the most reactive forms of oxygen, protecting unsaturated fatty acids from oxidation 5 . It is absolutely necessary that patients with the short bowel syndrome receive the essential fat soluble vitamins to avoid serious health problems. The fat soluble vitamins, A, D, E, and K are entirely hydrophobic compounds and are soluble only in lipids 5 . The nonpolar structure of the vitamins permit them from not interacting with water. The fat soluble vitamins can be readily incorporated into the hydrophobic interior of liposomes in a manner similar to their packaging into chylomicrons by intestinal epithelial cells. Rationale for the Incorporation of Cobalamin (vitamin B 12 ) into the Aqueous Compartment of Liposomes for its Delivery into the Blood of Patients With the Small Bowel Syndrome: Vitamin B 12 is not synthesized by humans. The major source of vitamin B 12 is from the diet 4 . Intrinsic factor, a glycoprotein produced by the gastric parietal cells, is required for B 12 absorbtion 4 . It complexes with B 12 (the extrinsic factor) and facilitates the absorption of the vitamin by cells of the of the ileum 4 . It was mentioned earlier that patients who have had their ileum resected cannot absorb vitamin B 12 . The malabsorbtion of vitamin B 12 causes hemopoietic problems in patients with the short bowel syndrome. The hemopoetic problems caused by a B 12 deficiency are identical to those observed in a folate deficiency secondary to (i.e., caused by) the B 12 deficiency 4 . The N 5 -methytetrahydrofolate cannot be converted to free FH 4 . Essentially, all of the folate becomes “trapped” as the N 5 -methyl derivatives. As the FH 4 pool is exhausted, deficiencies of the tetrahydrofolate derivatives needed for purine and dTMP biosynthesis develop leading to the characteristics of megaloblastic anemia 4 . B 12 deficiencies also cause neurological problems. It is absolutely necessary that patients who have the small bowel syndrome receive vitamin B 12 therapy periodically to prevent serious health problems. Vitamin B 12 is a water soluble vitamin and can be readily “trapped” in the aqueous compartment of liposomes and delivered directly to the liver where it is stored. Rationale for the Incorporation of Metal Ions (Ca 2&plus; , Mg 2&plus; , and Zn 2&plus; ) into the Aqueous Compartment of Liposomes for their Delivery into the Blood of Patients with the Small Bowel Syndrome. According to the literature, patients with the short bowel syndrome do not adequately absorb the metal ions, Ca 2&plus; , Mg 2&plus; , and Zn 2&plus; 1-3 . All of these ions are essential to the well being of all humans and must be part of their dietary intake. The body does not synthesize ions. They represent only a miniscule fraction of the weight of the human body. However, they are essential to human life because they are essential to the function of specific enzymes. These ions function as metal cofactors in the catalysis of many different biochemical actions that occur in the body. Calcium (Ca 2&plus; ) is also involved in hormone action and blood clotting. Calcium deficiency in the adult can result in bone loss. Magnesium activates many enzymes and also form a complex with ATP. Magnesium deficiencies can cause nausea, muscle weakness, irritability, and mental derangement. Zinc deficiency can cause dwarfism, loss of appetite, growth retardation, and hypogonadism. Patients who have had their ileum resected are at great risk for malnutrition. They require ongoing non-parenteral nutritional support to replace the nutrients they cannot absorb. In addition, any single nutritional deficit predisposes them to a host of serious medical conditions, for example, infections, reproductive failure, anemia, neurological abnormalities, growth retardation, skin disorders, and etc. Therefore, it is absolutely necessary that patients with the short bowel syndrome receive daily or periodically all of the nutrients they cannot absorb from their diets. It is paramount that pediatric patients with the small bowel syndrome receive the nutrients they cannot absorb to avoid retardation in growth and reproduction. The current art of liposome technology can provide a safe, effective, and efficient vehicular means of delivering the nutrients that cannot be absorbed in patients with the short bowel syndrome. The nutrients can be commercially packaged into liposomes singly, in various combinations, or all of them together and delivered simultaneously into the blood. The state of art of liposome technology has allowed it to develop oral foams 14-15 . There are areas in the mouth or the back of the throat that will absorb the nutrient-loaded liposome foam directly into the blood. The invention focuses on the delivery of certain nutrients via liposomes to patients with the short bowel syndrome. However, liposomes can be used to deliver the same or other nutrients to patients who have a diseased or a compromised gut. 
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