Complex coacervate for controlled release and related methods
Provided herein are coacervate compositions including cytokines, and methods of making and using the same. The coacervate can be formed by the mixing of an active agent, such as a drug or protein with the polyanion, such as heparin or heparan sulfate, and a custom-made polycation (e.g., PEAD or PELD). The coacervates can be used in the treatment of diseases and disorders where targeted treatment is desired, for example in treatment of cancers.
1. A composition comprising a complex or coacervate of a polycationic polymer, a polyanionic polymer, FGF2, and IL-10 in amounts effective to reduce myocardial fibrosis in a patient following a myocardial infarction.
2. The composition of claim 1 , wherein the polyanionic polymer is a heparin or heparan sulfate.
3. The composition of claim 1 , wherein the polycationic polymer is a copolymer comprising a polyester backbone comprising a copolymer of ethylene glycol diglyceride and either aspartic acid or glutamic acid, and pendant arginine groups.
4. The composition of claim 3 , wherein the polycationic polymer has a polydispersity index of less than 3.0.
5. The composition of claim 1 , in which the ratio of the polycationic polymer to the polyanionic polymer in the composition results in a neutral charge.
6. The composition of claim 1 , embedded in a hydrogel.
7. A method of delivering an interferon to a patient in need thereof, comprising administering the composition of claim 1 to the patient.
8. A method of treating a myocardial infarct in a patient, comprising, delivering to the myocardium at or adjacent to the infarct the composition of claim 1 in an amount effective to reduce myocardial fibrosis in the patient.
9. The composition of claim 1 , in which the ratio of the polycationic polymer to the polyanionic polymer in the composition results in a negative charge.
10. The composition of claim 1 , in which the ratio of the polycationic polymer to the polyanionic polymer in the composition results in a positive charge.
11. The composition of claim 1 , wherein the polycationic polymer is a copolymer comprising a polyester backbone comprising a copolymer of ethylene glycol diglyceride and either aspartic acid or glutamic acid, and pendant lysine groups.
12. The composition of claim 1 , wherein the polycationic polymer is poly(ethylene arginylaspartate diglyceride).
13. The composition of claim 1 , wherein the polycationic polymer is poly(ethylene lysinlyaspartate diglyceride).