Pharmaceutical preparation of carbohydrates for therapeutic use

Abstract

The disclosure provides methods for preparation of carbohydrate replacement therapies (CRT) that include nanocarriers of carbohydrates and glycolipids for pharmaceutical delivery to cell interior, endoplasmic reticulum, and Golgi for treating CDG type I and CDG type II diseases as well as other metabolic disorders.

1 - 20 . (canceled) 
     
     
         21 . A method for treating a congenital disorder of glycosylation (CDG) in a human in need thereof, wherein the CDG is CDG-Ia, CDG-Ie, CDG-Ii, CDG-Ik, CDG-Io, CDG-Ip, or DPM2-CDG, the method comprising administering to the human a pharmaceutical composition comprising:
 (i) a liposome comprising one or more phospholipids conjugated to polyethylene glycol (PEG); and   (ii) one or more phosphorylated monosaccharide, phosphorylated disaccharide, phosphorylated oligosaccharide, or phosphorylated polysaccharide, or any combination thereof, encapsulated in the liposome.   
     
     
         22 . The method of  claim 21 , wherein the pharmaceutical composition further comprises at least one pharmaceutically acceptable carrier. 
     
     
         23 . The method of  claim 21 , wherein the pharmaceutical composition is administered to the human intravenously. 
     
     
         24 . The method of  claim 21 , wherein the PEG minimizes degradation of the liposome, enhances retention of the liposome, or makes the liposome immunotolerant when administered to a human in need thereof, or any combination thereof. 
     
     
         25 . The method of  claim 21 , wherein the PEG is present at a molecular weight concentration between about 0.5 molar percent and about 20 molar percent. 
     
     
         26 . The method of  claim 21 , wherein the PEG is present at a molecular weight concentration between about 1 molar percent and about 8 molar percent. 
     
     
         27 . The method of  claim 21 , wherein one or more of the phospholipids comprise a polar head group. 
     
     
         28 . The method of  claim 21 , wherein one or more of the phospholipids comprise choline, ethanolamine, serine, glycerol, or inositol, or any combination thereof. 
     
     
         29 . The method of  claim 21 , wherein one or more of the phospholipids comprise phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylglycerol (PG), or phosphatidylinositol (PI), or any combination thereof. 
     
     
         30 . The method of  claim 21 , wherein one or more of the phospholipids comprise phosphatidylcholine (PC) or phosphatidylethanolamine (PE), or any combination thereof. 
     
     
         31 . The method of  claim 21 , wherein the liposome further comprises one or more glycerolipids or sphingolipids, or any combination thereof. 
     
     
         32 . The method of  claim 21 , wherein the liposome further comprises cholesterol, a fatty acid, or any combination thereof. 
     
     
         33 . The method of  claim 21 , wherein the pharmaceutical composition comprises: (ii) one or more phosphorylated monosaccharide encapsulated in the liposome. 
     
     
         34 . The method of  claim 21 , wherein the pharmaceutical composition comprises: (ii) one or more phosphorylated mannose, phosphorylated mannofuranose, or phosphorylated mannopyranose, or any combination thereof, encapsulated in the liposome. 
     
     
         35 . The method of  claim 21 , wherein the pharmaceutical composition comprises: (ii) mannose-1-phosphate encapsulated in the liposome. 
     
     
         36 . The method of  claim 35 , wherein the CDG is CDG-Ia. 
     
     
         37 . The method of  claim 35 , wherein the CDG is CDG-Ie. 
     
     
         38 . The method of  claim 35 , wherein the CDG is CDG-Ii. 
     
     
         39 . The method of  claim 35 , wherein the CDG is CDG-Ik. 
     
     
         40 . The method of  claim 35 , wherein the CDG is CDG-Io. 
     
     
         41 . The method of  claim 35 , wherein the CDG is CDG-Ip. 
     
     
         42 . The method of  claim 35 , wherein the CDG is DPM2-CDG. 
     
     
         43 . The method of  claim 35 , wherein:
 the PEG is present at a molecular weight concentration between about 0.5 molar percent and about 20 molar percent; and   one or more of the phospholipids comprise choline, ethanolamine, serine, glycerol, or inositol, or any combination thereof.   
     
     
         44 . The method of  claim 43 , wherein the PEG is present at a molecular weight concentration between about 1 molar percent and about 8 molar percent. 
     
     
         45 . The method of  claim 43 , wherein one or more of the phospholipids comprise phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylglycerol (PG), or phosphatidylinositol (PI), or any combination thereof. 
     
     
         46 . The method of  claim 43 , wherein one or more of the phospholipids comprise phosphatidylcholine (PC) or phosphatidylethanolamine (PE), or any combination thereof. 
     
     
         47 . A pharmaceutical composition, comprising:
 (i) a lipid particle comprising one or more phospholipids conjugated to polyethylene glycol (PEG); and   (ii) a nucleotide sugar, a uridine diphosphate, a guanine diphosphate, a cytosine monophosphate, fucose, GDP-fucose, a sialic acid, CMP-sialic acid, N-acetylneuraminic acid (Neu5Ac), CMP-Neu5Ac or any combination thereof, encapsulated in the lipid particle.   
     
     
         48 . A method for treating a congenital disorder of glycosylation (CDG) in a human in need thereof, comprising administering to the human a pharmaceutical composition of  claim 47 . 
     
     
         49 . The method of  claim 48 , wherein the CDG is CDG-Ia, CDG-Ie, CDG-Ii, CDG-Ik, CDG-Io, CDG-Ip, or DPM2-CDG.