Reversible masking of liposomal complexes for targeted delivery
The present invention is a composition and process for avoiding non-specific uptake of targeted liposomal complexes in the lung and other highly vascular issues. The reversible masking of liposomal complexes allows increased delivery of nucleic acid molecules to target cells or tissues.
1. A targeted liposomal complex comprising:
a cationic liposome having an internal lipid bilayer and an external lipid bilayer;
a pharmaceutical encapsulated between the internal lipid bilayer and the external lipid bilayer;
a targeting ligand associated with an exterior surface of the external lipid bilayer of the cationic liposome; and
a masking agent reversibly associated with the exterior surface of the external bilayer, wherein the masking agent is n-dodecyl-β-D-maltopyranoside.
2. The liposomal complex of claim 1 , wherein a dissociation constant of the masking agent with the exterior surface of the lipid layer is greater than a dissociation constant of the targeting ligand with the exterior surface of the lipid layer.
3. The liposomal complex of claim 1 , wherein the masking agent has a molecular weight that is less than a molecular weight of the targeting ligand.
4. The liposomal complex of claim 1 , wherein the pharmaceutical includes a polynucleotide.
5. The liposomal complex of claim 1 , wherein the pharmaceutical is a plasmid.
6. The liposomal complex of claim 1 , wherein the pharmaceutical includes a peptide.
7. The liposomal complex of claim 1 , wherein the cationic liposome has a pair of internal lipid bilayers and a pair of external lipid bilayers.
8. The liposomal complex of claim 1 , wherein the cationic liposome is a bilamellar invaginated liposome comprising an extruded mixture of DOTAP and cholesterol.
9. The liposomal complex of claim 1 , wherein the targeting ligand has a molecular weight ranging from about 500 daltons to about 5,000 daltons.
10. The liposomal complex of claim 1 , wherein the concentration of the masking agent ranges from about 3 mM to about 10 mM.
11. A targeted liposomal complex comprising:
a cationic liposome having an internal lipid bilayer and an external lipid bilayer;
a pharmaceutical encapsulated between the internal lipid bilayer and the external lipid bilayer;
a targeting ligand associated with an exterior surface of the external lipid bilayer of the cationic liposome; and
a masking agent reversibly associated with the exterior surface of the external bilayer, wherein the masking agent is a pendant modified polyethylene glycol NHS ester having five pendant carboxyl groups located along the backbone of the polyethylene glycol chain and a molecular weight of about 5,000 daltons.
12. The liposomal complex of claim 11 having a zeta potential that is less than 16 millivolts.
13. The liposomal complex of claim 11 having a zeta potential ranging from about 3 millivolts to about 10 millivolts.
14. The liposomal complex of claim 11 having a mean particle size between about 200 nanometers and about 500 nanometers.
15. A liposomal complex for drug delivery, the liposomal complex comprising:
a pharmaceutical surrounded and protected by a cationic lipid layer; and
a masking agent consisting of n-dodecyl-β-D-maltopyranoside reversibly associated with an exterior surface of the lipid layer, wherein the masking agent inhibits first-pass clearance of the liposomal complex by a lung tissue.
16. The liposomal complex of claim 15 , further comprising a targeting ligand associated with the exterior surface of the lipid layer.
17. The liposomal complex of claim 16 , wherein a dissociation constant of the masking agent with the exterior surface of the lipid layer is greater than a dissociation constant of the targeting ligand with the exterior surface of the lipid layer.
18. The liposomal complex of claim 16 , wherein the masking agent has a molecular weight that is less than a molecular weight of the targeting ligand.
19. The liposomal complex of claim 15 wherein the pharmaceutical includes a polynucleotide.
20. The liposomal complex of claim 19 , wherein the pharmaceutical is a plasmid.
21. The liposomal complex of claim 15 , wherein the pharmaceutical includes a peptide.
22. The liposomal complex of claim 15 having a zeta potential that is less than 16 millivolts.
23. The liposomal complex of claim 15 having a zeta potential ranging from about 3 millivolts to about 10 millivolts.
24. The liposomal complex of claim 15 having a mean particle size between about 200 nanometers and about 500 nanometers.