Mucosal delivery of therapeutic molecules, proteins, or particles coupled to ceramide lipids
Described herein are compositions and methods useful for allowing for the absorption (passage) of agents of interest, such as therapeutic agents, across epithelial and mucosal barriers and/or into certain subcellular compartments of the cell, such as the recycling endosome (RE), Golgi, and the endoplasmic reticulum (ER).
1. A delivery vehicle comprising a glycosphingolipid and an agent to be delivered, wherein the glycosphingolipid comprises a ceramide that comprises (a) a short chain fatty acid (C4-C12) or (b) a long chain fatty acid (C14-C28) comprising at least one cis double bond between two carbon atoms and the agent to be delivered is attached to the oligosaccharide of the glycospingolipid.
2. The delivery vehicle of claim 1 , wherein the glycosphingolipid is monosialotetrahexosylganglioside (GM1).
3. The delivery vehicle of claim 1 , wherein the fatty acid is a C12 fatty acid with no double bonds between carbon atoms or a C16 fatty acid comprising a cis double bond.
4. The delivery vehicle of claim 1 , wherein the agent to be delivered is selected from the group consisting of proteins, peptides, nucleic acids, polysaccharides and carbohydrates, lipids, glycoproteins, and combinations thereof and synthetic organic and inorganic drugs exerting a biological effect when administered to a subject.
5. The delivery vehicle of claim 1 , wherein the agent to be delivered is a therapeutic agent.
6. A glycosphingolipid-therapeutic agent complex comprising a glycosphingolipid attached to a therapeutic agent, wherein the fatty acid of the ceramide comprises (a) 4-12 carbon atoms or (b) 14-28 carbon atoms with at least one cis double bond between two carbon atoms and wherein the therapeutic agent is attached to the oligosaccharide of the glycosphingolipid.
7. The glycosphingolipid-therapeutic agent complex of claim 6 , wherein the ganglioside is monosialotetrahexosylganglioside (GM1).
8. The glycospingolipid-therapeutic agent complex of claim 6 , wherein the fatty acid is a C12 fatty acid with no double bonds between carbon atoms or a C16 fatty acid comprising a cis double bond.
9. The glycosphingolipid-therapeutic agent complex of claim 6 , wherein the agent to be delivered is selected from the group consisting of proteins, peptides, nucleic acids, carbohydrates, lipids, glycoproteins, and combinations thereof and synthetic organic and inorganic drugs exerting a biological effect when administered to a subject.
10. A glycosphingolipid-therapeutic agent complex, wherein the glycosphingolipid comprises a ceramide that comprises (a) a short chain (C4-C12) fatty acid or (b) a long chain (C14-C28) fatty acid comprising a cis double bond and the therapeutic agent is attached to the oligosaccharide of the glycosphingolipid.
11. The ganglioside-therapeutic agent complex of claim 10 , wherein the glycosphingolipid is monosialotetrahexosylganglioside (GM1).
12. The glycosphingolipid-therapeutic agent complex of claim 10 , wherein the fatty acid is a C12 fatty acid with no double bonds between carbon atoms or a C16 fatty acid comprising a cis double bond.
13. The glycosphingolipid-therapeutic agent complex of claim 10 , wherein the agent to be delivered is selected from the group consisting of proteins, peptides, nucleic acids, polysaccharides and carbohydrates, lipids, glycoproteins, and combinations thereof and synthetic organic and inorganic drugs exerting a biological effect when administered to a subject.
14. A ganglioside-therapeutic agent complex comprising monosialotetrahexosylganglioside (GM1) attached to a therapeutic agent, wherein the fatty acid component of the ceramide comprises (a) 4-12 carbon atoms with no double bonds between carbon atoms or (b) 14-28 carbon atoms comprising at least one cis double bond between two carbon atoms and the therapeutic agent is attached to the oligosaccharide of monosialotetrahexosylganglioside (GM1).
15. A composition comprising a delivery vehicle of claim 1 and a pharmaceutically acceptable composition.
16. A composition comprising a glycosphingolipid-therapeutic agent complex of claim 6 and a pharmaceutically acceptable composition.
17. The delivery vehicle of claim 5 , wherein the therapeutic agent comprises active GLP1 peptide hormone.