Lipid-based coating composition, and an object having a lipid-based coating
A lipid-based coating composition for coating a medical device, wherein the coating composition includes a) lipid vesicles consisting of i. 85-95 mol % of a phospholipid (A) having a phosphatidylcholine group; ii. 5-12 mol % of a PEGylated phospholipid (B); optionally 0-3 mol % of a lipophilic compound (C) other than lipids (A) and (B); b) 0-5 wt. % of a water-soluble additive (D); and c) at least 95 wt. % of water, wherein lipid vesicles having a number average size between 50 and 140 nm (measured according to dynamic light scattering) and wherein the lipid vesicle concentration ranges between 0.025 mg/ml and 2 mg/ml, and wherein the mol % of lipids (A), (B) and (C) is calculated relative to the total molar amount of lipids (A)+(B)+(C) in the lipid-based coating composition and wherein the wt. % of water-soluble additive (D) is calculated relative to the weight of the total composition.
1. A lipid-based coating composition for coating a medical device, wherein the composition comprises:
i) lipid vesicles consisting of
85-95 mol % of a phospholipid (A) having a phosphatidylcholine group;
5-12 mol % of a PEGylated phospholipid (B);
optionally 0-3 mol % of a lipophilic compound (C) other than lipids the phospholipid (A) and the PEGylated phospholipid (B);
0-5 wt. % of a water-soluble additive (D);
il) at least 95 wt. % of water, and
iii) an alcohol,
wherein the lipid vesicles have a number average size between 50 and 140 nm measured according to dynamic light scattering,
wherein a concentration of the lipid vesicles ranges between 0.025 mg/ml and 2 mg/ml in the composition, and
wherein the mol % of the phospholipid (A), the PEGylated phospholipid (B) and the lipophilic compound (C) is calculated relative to the total molar amount of (A)+(B)+(C) in the composition, wherein the wt. % of water-soluble additive (D) and the wt. % of water are calculated relative to the weight of the total composition.
2. The composition according to claim 1 , wherein the phospholipids (A) are chosen from 1,2-didecanoyl-sn-glycero-3-phosphocholine (DDPC), 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-dierucoyl-sn-glycero-3-phosphocholine (DEPC), a DiynePC lipid, 1,2-bis (10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine and 1-palmitoyl-2-(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine.
3. The composition according to claim 2 , wherein the PEGylated phospholipids (B) are chosen from the group consisting of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-350] (DSPE-PEG350), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-550] (DSPE-PEG550), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-750] (DSPE-PEG750), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-1000] (DSPE-PEG1000), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000] (DSPE-PEG3000), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000] (DSPE-PEG5000), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-350] (DOPE-PEG350), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-550] (DOPE-PEG550), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-750] (DOPE-PEG750), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-1000] (DOPE-PEG1000), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DOPE-PEG2000), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000] (DOPE-PEG3000), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000] (DOPE-PEG5000), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-350] (DPPE-PEG350), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-550] (DPPE-PEG550), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-750] (DPPE-PEG750), and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-1000] (DPPE-PEG1000), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DPPE-PEG2000),
wherein the lipophilic compound (C) is chosen from phosphatidic acid derivatives, phosphatidylglycerol derivatives, phosphatidylethanolamine derivatives, phosphatidylserine derivatives, natural phospholipid derivates, sterols, cholesterol, desmosterol, lanosterol and derivatives of sterols, polyglycerin-phospholipids, functionalized-phospholipids, terminal activated-phospholipids), N-[1-(2,3-Dioleoyloxy) propyl]-N,N,N-trimethylammonium methyl-sulfate (DOTAP), proteins, peptides, amphiphiles, ionic polymers, sugar molecules, enzymes, active pharmaceutical components and non-active pharmaceutical components, and
wherein the water-soluble additive (D) is chosen from the group of salts, buffers, (poly) electrolytes and complexing agents.
4. The composition according to claim 1 , wherein phospholipids (A) are chosen from the group consisting of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC).
5. The composition according to claim 4 , wherein the PEGylated phospholipids (B) are chosen from the group consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DPPE-PEG2000) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DOPE-PEG2000),
wherein the lipophilic compound (C) is chosen from Phosphatidic acid derivatives, Phosphatidylglycerol derivatives, Phosphatidylethanolamine derivatives, Phosphatidylserine derivatives, natural phospholipid derivates, Sterols, cholesterol, desmosterol, lanosterol and derivatives of sterols, polyglycerin-phospholipids, functionalized-phospholipids, terminal activated-phospholipids), N-[1-(2,3-Dioleoyloxy) propyl]-N, N, N-trimethylammonium methyl-sulfate (DOTAP), proteins, peptides, amphiphiles, ionic polymers, sugar molecules, enzymes, active pharmaceutical components and non-active pharmaceutical components, and
wherein the water-soluble additive (D) is chosen from the group of salts, buffers, (poly) electrolytes and complexing agents.
6. The composition according to claim 1 , wherein the phospholipids (A) are chosen from the group consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC).
7. The composition according to claim 6 , wherein the PEGylated phospholipids (B) are chosen from the group consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DPPE-PEG2000) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DOPE-PEG2000),
wherein the lipophilic compound (C) is chosen from phosphatidic acid derivatives, phosphatidylglycerol derivatives, phosphatidylethanolamine derivatives, phosphatidylserine derivatives, natural phospholipid derivates, sterols, cholesterol, desmosterol, lanosterol and derivatives of sterols, polyglycerin-phospholipids, functionalized-phospholipids, terminal activated-phospholipids), N-[1-(2,3-Dioleoyloxy) propyl]-N,N,N-trimethylammonium methyl-sulfate (DOTAP), proteins, peptides, amphiphiles, ionic polymers, sugar molecules, enzymes, active pharmaceutical components and non-active pharmaceutical components, and
wherein the water-soluble additive (D) is chosen from phosphate buffered saline (PBS), HEPES, NaCl 2 and CaCl 2 ).
8. The composition according to claim 1 , wherein the PEGylated phospholipids (B) are chosen from the group consisting of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-350] (DSPE-PEG350), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-550] (DSPE-PEG550), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-750] (DSPE-PEG750), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-1000] (DSPE-PEG1000), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000] (DSPE-PEG3000), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000] (DSPE-PEG5000), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-350] (DOPE-PEG350), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-550] (DOPE-PEG550), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-750] (DOPE-PEG750), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-1000] (DOPE-PEG1000), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DOPE-PEG2000), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000] (DOPE-PEG3000), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000] (DOPE-PEG5000), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-350] (DPPE-PEG350), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-550] (DPPE-PEG550), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-750] (DPPE-PEG750), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-1000] (DPPE-PEG1000), and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DPPE-PEG2000).
9. The composition according to claim 1 , wherein the PEGylated phospholipids (B) are chosen from the group consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DPPE-PEG2000) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DOPE-PEG2000).
10. The composition according to claim 1 , wherein the lipophilic compound (C) is chosen from phosphatidic acid derivatives, phosphatidylglycerol derivatives, phosphatidylethanolamine derivatives, phosphatidylserine derivatives, natural phospholipid derivates, sterols, cholesterol, desmosterol, lanosterol and derivatives of sterols, polyglycerin-phospholipids, functionalized-phospholipids, terminal activated-phospholipids, N-[1-(2,3-Dioleoyloxy) propyl]-N,N,N-trimethylammonium methyl-sulfate (DOTAP), proteins, peptides, amphiphiles, ionic polymers, sugar molecules, enzymes, active pharmaceutical components and non-active pharmaceutical components.
11. The composition according to claim 1 , wherein the water-soluble additive (D) is chosen from the group of salts, buffers, (poly) electrolytes and complexing agents.
12. A medical device comprising the composition according to claim 1 , wherein the medical device is a contact lens, a catheter, or a medical implant.
13. A medical device comprising the composition according to claim 3 , wherein the medical device is a contact lens, a catheter, or a medical implant.
14. The composition according to claim 1 , wherein the alcohol is ethanol.
15. A method, comprising the step of:
applying the composition of claim 1 on a substrate or repairing defects in a lipid on a substrate with the coating composition of claim 1 .