Hyperbranched polyglycerol-coated particles and methods of making and using thereof
Core-shell particles and methods of making and using thereof are described herein. The core is formed of or contains one or more hydrophobic materials or more hydrophobic materials. The shell is formed of or contains hyperbranched polyglycerol (HPG). The HPG coating can be modified to adjust the properties of the particles. Unmodified HPG coatings impart stealth properties to the particles which resist non-specific protein absorption and increase circulation in the blood. The hydroxyl groups on the HPG coating can be chemically modified to form functional groups that react with functional groups and adhere the particles to tissue, cells, or extracellular materials, such as proteins.
1. Particles having a diameter between about 25 nm and about 250 nm comprising
(a) a core comprising one or more hydrophobic biodegradable polymers; and
(b) a shell comprising hyperbranched polyglycerol, wherein the hyperbranched polyglycerol is covalently bound to the hydrophobic biodegradable polymer, and
and wherein the hyperbranched polyglycerol comprises a plurality of surface hydroxyl groups and vicinal diol groups which decrease uptake of the particles by phagocytic cells following administration to an individual.
2. The particles of claim 1 , wherein the biodegradable polymer is an aliphatic polyester.
3. The particles of claim 2 , wherein the aliphatic polyester is selected from the group consisting of poly(lactic acid), poly(glycolic acid), and copolymers thereof.
4. The particles of claim 3 , wherein the aliphatic polyester is polylactic acid.
5. The particles of claim 1 , wherein the hyperbranched polyglycerol is covalently bound to the one or more hydrophobic materials.
6. The particles of claim 1 , further comprising one or more agents selected from the group consisting of therapeutic agents, diagnostic agents, prophylactic agents, nutraceutical agents, and combinations thereof.
7. The particles of claim 6 , wherein the one or more agents are encapsulated within the particle, associated with the surface of the particle, or combinations thereof.
8. The particles of claim 7 , wherein the one or more agents are encapsulated within the particle.
9. The particles of claim 1 , wherein the particle further comprises one or more targeting agents.
10. The particles of claim 9 , wherein the one or more targeting agents are covalently bound to the shell.
11. The particles of claim 1 , wherein the average diameter of the particles is about 100 nm.
12. A pharmaceutical composition comprising the particles of claim 1 and one or more pharmaceutically acceptable carriers.
13. The composition of claim 12 , wherein the one or more carriers are suitable for parenteral administration.
14. The composition of claim 12 , wherein the one or more carriers are suitable for enteral administration.
15. The composition of claim 12 , wherein the one or more carriers are suitable for topical administration.
16. A method for delivering one or more agents selected from the group consisting of therapeutic agents, diagnostic agents, prophylactic agents, nutraceuticals agents, and combinations thereof to a patient in need thereof, the method comprising administering an effective amount of the composition of claim 12 , wherein the one or more agents are encapsulated within the particle, associated with the surface of the particle, or a combination thereof.
17. The particles of claim 1 , wherein the surface hydroxyl group density is at least about 1, 2, 3, 4, 5, 6, 7, or 8 hydroxyl groups/nm 2 .
18. The particles of claim 9 , wherein the targeting group density on the shell is at least about 1, 2, 3, 4, 5, 6, 7, or 8 targeting groups/nm 2 .