Lipid substitution on aminoglycoside based polymers: plasmid delivery, anticancer drug delivery and transgene expression
A method to form a lipid-containing aminoglycoside-based polymer, where the method includes reacting an aminoglycoside with a diepoxide to form an aminoglycoside-based polymeric material, and then reacting the aminoglycoside-based polymeric material with an acyl chloride to form the lipid-containing aminoglycoside-based polymer.
1. A method to form an aminoglycoside based polymer, comprising:
reacting an aminoglycoside having a structure:
wherein R 1 is an aminoglycoside monomer, with a diepoxide having a structure:
wherein R 2 is a backbone of said diepoxide, to form an aminoglycoside-based polymeric material having a structure:
wherein n is between about 3 and about 10.
2. The method of claim 1 , further comprising reacting said aminoglycoside-based polymeric material with an acyl chloride having a structure:
wherein R 3 is an alkyl group comprising C 6 , C 14 , or C 18 , to form a lipid-containing aminoglycoside polymer having a structure:
3. The method of claim 1 , wherein said aminoglycoside comprises neomycin.
4. The method of claim 1 , wherein said aminoglycoside comprises paromomycin.
5. The method of claim 1 , wherein said aminoglycoside comprises apramycin.
6. The method of claim 1 , wherein said diepoxide comprises glycerol diglycidyl ether.
7. The method of claim 1 , wherein said diepoxide comprises resorcinol diglycidyl ether.
8. The method of claim 2 , wherein the molar ratio of said acyl chloride to said aminoglycoside-based polymeric material is about 1:2.
9. The method of claim 2 , wherein the molar ratio of said acyl chloride to said aminoglycoside-based polymeric material is about 1:5.
10. The method of claim 2 , wherein the molar ratio of said acyl chloride to said aminoglycoside-based polymeric material is about 1:10.
11. The method of claim 2 , wherein R 3 comprises a C6 hydrocarbon.
12. The method of claim 2 , wherein R 3 comprises a C18 hydrocarbon.
13. A lipid-conjugated polymer, coprising:
wherein R 1 is an aminoglycoside monomer, R 2 is a backbone of a diepoxide, and R 3 is an alkyl group comprising C6, C14, or C18.
14. A method to form an aminoglycoside based polymer, comprising:
reacting an aminoglycoside with a diepoxide in a solvent system of DMSO to form an aminoglycoside-based polymeric material.
15. The method of claim 14 , further comprising reacting said aminoglycoside-based polymeric material with an acyl chloride to form a lipid-containing aminoglycoside polymer.
16. The method of claim 14 , wherein the diepoxide comprises diglycidyl ether.