Topical formulation of hyperbranched polyglycerol-coated particles thereof

Patent metadata

Field	Value
Publication number	US-10758459-B2
Application number	US-201916379224-A
Country	US
Kind code	B2
Filing date	Apr 9, 2019
Priority date	May 9, 2014
Publication date	Sep 1, 2020
Grant date	Sep 1, 2020

Abstract

Core-shell particles have a hydrophobic core and a shell formed of or containing hyperbranched polyglycerol (HPG). The HPG can be covalently bound to the one or more materials that form the core or coated thereon. The HPG coating can be modified to adjust the properties of the particles. For example, unmodified HPG coatings impart stealth properties to the particles which resist non-specific protein absorption. Alternatively, the hydroxyl groups on the HPG coating can be chemically modified to form functional groups that react with functional groups on tissue or otherwise interact with tissue to adhere the particles to the tissue, cells, or extracellular materials, such as proteins. Such functional groups include, but not limited to, aldehydes, amines, and O-substituted oximes. Topical formulation for application to the skin contain these HPG coated nanoparticles. In some embodiments, the particles include therapeutic, diagnostic, nutraceutical, and/or prophylactic agents such as those used as sunblock compositions.

First claim

We claim:

1. A method of adhering particles to a tissue, the method comprising administering particles comprising:
a hydrophobic polymer core and a shell comprising hyperbranched polyglycerol covalently bound to the hydrophobic polymer of the hydrophobic polymer core;
wherein the hyperbranched polyglycerol is functionalized with one or more reactive functional groups, or functional groups having tissue targeting moieties bound thereto, or a combination thereof, wherein the one or more reactive functional groups are bound to the hyperbranched polyglycerol through its vicinal hydroxyl moieties or through a chemical transformation of its vicinal hydroxyl moieties;
wherein the one or more reactive functional groups and the functional groups having tissue targeting moieties bound thereto adhere to tissue, cells, or proteins; and
one or more agents selected from agents protecting the skin from ultraviolet light, therapeutic agents, diagnostic agents, prophylactic agents, and combinations thereof;
wherein the one or more agents are encapsulated within the particles, associated with the surface of the particles, or a combination thereof.

2. The method of claim 1 , wherein the hydrophobic polymer core comprises a biodegradable hydrophobic polymer.

3. The method of claim 2 , wherein the biodegradable hydrophobic polymer is selected from the group consisting of polyhydroxyalkanoates, poly(hydroxy acids), polyanhydrides, polyorthoesters, copolymers and blends thereof, poly(lactic acid), poly(glycolic acid), and copolymers thereof.

4. The method of claim 1 , wherein the hyperbranched polyglycerol has tissue targeting moieties bound to the reactive functional groups.

5. The method of claim 1 , wherein the one or more reactive functional groups are selected from the group consisting of aldehydes, amines, O-substituted oximes, and combinations thereof.

6. The method of claim 1 , wherein the one or more agents protect the skin from ultraviolet light.

7. The method of claim 1 , wherein the one or more agents are encapsulated within the particles.

8. The method of claim 1 , wherein the one or more agents are associated with the surface of the particles.

9. The method of claim 1 , wherein the one or more agents are encapsulated within the particles and associated with the surface of the particles.

10. The method of claim 1 , wherein the one or more agents are filters of or block ultraviolet light.

11. The method of claim 10 , wherein the one or more agents are selected from the group consisting of zinc oxide (ZnO), titanium dioxide (TiO 2 ), avobenzone, tinosorb S, mexoryl SX, mexoryl XL, helioplex, octinoxate, octocrylene, oxybenzone, octisalate, homosalate, uvinul T 150, cinoxate, aminobenzoic acid, padimate 0, ensulizole, dioxybenzone, meradimate, sulisobenzone, trolamine salicylate, enzacamene, bisdisulizole disodium, uvinul A Plus, uvasorb HEB, parsol SLX, amiloxate, and combination thereof.

12. The method of claim 1 , wherein the particles are in a formulation comprising a carrier suitable for topical administration.

13. The method of claim 1 , wherein the particles are designed to release one or more therapeutic agents, diagnostic agents, prophylactic agents, nutraceuticals, or combinations thereof over a period of hours to weeks.

14. The method of claim 1 , wherein the particles contain different types of molecules encapsulated within the particles, attached to the surface of the particles, or a combination thereof.

15. The method of claim 1 , wherein the particles contain both targeting agents and one or more agents selected from the group consisting of therapeutic agents, diagnostic agents, prophylactic agents and nutraceuticals.

16. The method of claim 1 , wherein the particles are modified to adhere specifically to one or more target molecules associated with a target selected from the group consisting of organs, tissues, cells and extracellular matrix.

17. The method of claim 1 , wherein the particles are in a topical formulation for application to the skin, cornea, orifice or mucosa.

18. The method of claim 17 , wherein the particles release different therapeutic agents, diagnostic agents, prophylactic agents, nutraceuticals, or combinations thereof, wherein the therapeutic agents, diagnostic agents, prophylactic agents, nutraceuticals, or combinations thereof are encapsulated within the particles, attached to the surface of the particles, or a combination thereof.

19. The method of claim 17 , wherein the particles release different amounts or different therapeutic agents, diagnostic agents, prophylactic agents, nutraceuticals, or combinations thereof at same time or at different times.

20. The method of claim 17 , wherein the particles comprise a combination of different targeting agents encapsulated within the particles, surrounded by the particles, distributed throughout the particles, or a combination thereof.

21. The method of claim 1 , wherein the agent is selected from the group consisting of antibiotics, antivirals, anti-parasites, chemotherapeutics, peptide drugs, anti-inflammatories, and nutraceuticals.

22. The method of claim 21 wherein the agent is a chemotherapeutic selected from the group consisting of doxorubicin, cyclosporine, mitomycin C, cisplatin and carboplatin, BCNU, 5FU, methotrexate, adriamycin, camptothecin, epothilones A-F, and taxol.

Assignees

• Univ Yale

Inventors

• Deng Yang
• Ediriwickrema Asiri
• Saltzman William M

Classifications

• A61K31/4178 Primary

  not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin · CPC title

• A61K39/00

  Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53) · CPC title

• A61K47/6937

  the polymer being PLGA, PLA or polyglycolic acid · CPC title

• A61K47/62

  the modifying agent being a protein, peptide or polyamino acid · CPC title

• A61P35/00

  Antineoplastic agents · CPC title