Mucosal delivery of therapeutic molecules, proteins, or particles coupled to ceramide lipids
AssigneeChildren's Medical Center Corporation
InventorsWayne I. Lencer, Daniel J F Chinnapen, Randy Mrsny
Life of this patent
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Abstract
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).
Claims21
A method of delivering an agent into cells or across a mucosal surface, comprising contacting a complex of a delivery vehicle and the agent with the cells or the mucosal surface, under conditions appropriate for uptake of the delivery vehicle or the agent of interest into the cell or absorption of the delivery vehicle or the agent of interest across the mucosal surface,
- wherein the delivery vehicle comprises a glycosphingolipid that forms a complex with the agent to be delivered, wherein the glycosphingolipid comprises a ceramide consisting of a sphingosine coupled with (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 wherein the agent to be delivered is covalently attached to the oligosaccharide of the glycosphingolipid.
A method of delivering an agent into cells or across a mucosal surface, comprising contacting a ganglioside-therapeutic agent complex with the cells or the mucosal surface, under conditions appropriate for uptake of the ganglioside-therapeutic agent complex into the cell or absorption of the ganglioside-therapeutic agent complex across the mucosal surface,
- wherein the ganglioside-therapeutic agent complex comprises monosialotetrahexosylganglioside (GM1) attached to a therapeutic agent, wherein the GM1 comprises a ceramide consisting of a sphingosine coupled with a fatty acid of:
- (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 wherein the therapeutic agent is covalently attached to the oligosaccharide of monosialotetrahexosylganglioside (GM1).
A method of treating a disease or condition in an individual in need thereof, comprising administering an effective amount of a ganglioside-therapeutic agent complex to the individual,
- wherein the ganglioside-therapeutic agent complex comprises a glycosphingolipid and a therapeutic agent to be administered, wherein the glycosphingolipid comprises a ceramide that consists of a sphingosine coupled with:
- (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 wherein the therapeutic agent to be administered is covalently attached to the oligosaccharide of the glycosphingolipid, and
- wherein the effective amount is an amount sufficient to ameliorate/reduce the extent to which the disease or condition occurs in the individual.
Dependencies are inferred from the claim text.