Compositions of less immunogenic and long-circulating protein-lipid complexes
View Patent ↗Provided are lipidic particles comprising phosphatidylcholine, phosphatidylinositol and cholesterol. Also provided are compositions comprising the lipidic particles and having associated therewith therapeutic agents such as peptides, polypeptides or proteins. In these compositions, the therapeutic agents have reduced immunogenicity and/or longer circulating time. These compositions can be used for therapeutic administration of the peptides, polypeptides and/or proteins.
1. Lipidic particles comprising phosphatidylcholine (PC), phosphatidylinositol (PI) and cholesterol, wherein the ratio of PC to PI is between 60:40 to 40:60 and cholesterol is present between 5-15% of PC and PI together, the particles have a size of between 40 to 140 nm.
2. The particles of claim 1 , wherein the PC to PI ratio is between 55:45 and 45:55.
3. The particles of claim 2 , wherein the PC to PI ratio is 50:50.
4. The particles of claim 1 , wherein each acyl chains of PC and PI independently has between 12 and 22 carbon atoms, and is saturated or unsaturated.
5. The particles of claim 1 , wherein the particles are present in a lyophilized form.
6. The particles of claim 1 , wherein the PI is soy PI and PC is egg PC.
7. A composition comprising the lipidic particles of claim 1 , and further comprising one or more therapeutic agents associated therewith such that the immunogenicity of the therapeutic agent is reduced, wherein the therapeutic agent is a peptide, polypeptide or a protein.
8. The composition of claim 7 , wherein the therapeutic agent is a protein involved in the blood coagulation cascade.
9. The composition of claim 8 , wherein the therapeutic agent is selected from the group consisting of Factor VIII, Factor VII, Factor IX, Factor V, Willebrand Factor (vWF) and von Heldebrant Factor (vHF).
10. The composition of claim 7 wherein the therapeutic agent is selected from the group consisting of tissue plasminogen activator, insulin, growth hormone, erythropoietin alpha, VEG-F, thrombopoietin and lysozyme.
11. The composition of claim 7 , wherein at least 50% of the lipidic particles have a size of 140 nm or less.
12. The composition of claim 11 , wherein at least 60%, 70% 80% or 90% of the lipidic particles have a size of 140 nm or less.
13. The composition of claim 11 , wherein at least 50%, 60%, 70%, 80% or 90% of the lipidic particles have a size between 40 to 100 nm.
14. The composition of claim 11 , wherein the size of the lipidic particles is between 80 and 100 nm.
15. A method of reducing the immunogenicity of a therapeutic agent selected from the group consisting of a peptide, polypeptide or a protein comprising the steps of:
a) preparing the lipidic particles of claim 1 by extruding multilamellar vesicles comprising PC, PI and cholesterol through a sizing device to form lipidic particles of less than 140 nm; and
b) mixing the therapeutic agent with the lipidic particles prepared in step a) wherein the immunogenicity of the therapeutic agent is reduced.