Zwitterionic dendritic amphiphiles, zwitterionic dendrimers, zwitterionic telodendrimers, nanocarriers comprising same, and methods of making and using same
View Patent ↗Zwitterionic dendrimers and zwitterionic polymers and methods of making the zwitterionic dendrimers/polymers are provided herein. Also provided are amphiphilic dendrimers and amphiphilic telodendrimers with one or more zwitterionic dendron/polymer/linear group(s)/moiety(s) covalently bonded thereto. The amphiphilic dendrimers and amphiphilic telodendrimers are useful in protein binding and drug delivery. The amphiphilic dendrimers and amphiphilic telodendrimers are used in methods of treatment and/or imaging.
1. A Janus-type zwitterionic dendritic compound comprising the following structure:
p [(R z )-L z -]-D Z (X)-L-D(X)—[—(R)] y
wherein R Z is one or more zwitterionic groups selected from the group consisting of: a phosphorylcholine moiety (PC) and carboxybetain moiety (CB) wherein L Z is optional and is a linker glycerol-succinate moiety;
D z is a nonlinear dendritic polymer moiety having a single focal group and one or more branched monomer units (X), and a plurality of end groups, wherein (X) is independently selected from the group consisting of a diamino carboxylic acid moiety, a dihydroxy carboxylic acid moiety, and a hydroxyl amino carboxylic acid moiety;
L is optional and at least one linker group or a bond selected from the group consisting of a polyethylene glycol moiety, disulfide bond moiety and acid labile moiety;
D is a nonlinear dendritic polymer moiety having a single focal group and one or more branched monomer units (X), and a plurality of end groups, wherein (X) is independently selected from the group consisting of a diamino carboxylic acid moiety, a dihydroxy carboxylic acid moiety, and a hydroxyl amino carboxylic acid moiety
R is an end group of the D dendritic polymer moiety and is independently at each occurrence at least one compound selected from the group consisting of, riboflavin, chlorogenic acid, rhein, vitamin E, and cholesterol;
subscript p is an integer from 2 to 64; and
subscript y is an integer from 2 to 64; and
combinations thereof.
2. The compound of claim 1 , wherein R Z is glycerolphosphorylcholine, D z and D are nonlinear dendritic structures; X is lysine; L is
R is Rhein; subscript y is 4; subscript p is 8; and the compound has a molecular weight of 5436.30, an exact mass of 5433.15, and the chemical formula C232H353N33099P8.
3. The compound of claim 1 , wherein the compound further comprises a protein associated with the compound.
4. The compound of claim 1 , wherein the compound further comprises a drug associated with the compound.
5. A nanocarrier comprising a plurality of compounds of claim 1 .
6. The nanocarrier of claim 5 , wherein at least one of the compounds of the plurality compounds is structurally distinct from rest of the plurality of compounds.
7. The nanocarrier of claim 5 , wherein the nanocarrier further comprises one or more protein or peptides.
8. The nanocarrier of claim 5 , wherein the nanocarrier further comprises a drug.
9. The nanocarrier of claim 5 , wherein the nanocarrier further comprises an imaging agent.
10. A method of delivering a protein and/or drug to an individual comprising administering to the individual a compound of claim 1 .
11. A method of delivering a protein and/or drug to an individual comprising administering to the individual a nanocarrier of claim 5 .