Silk microspheres and methods for surface lubrication

Patent metadata

Field	Value
Publication number	US-10653786-B2
Application number	US-201314390351-A
Country	US
Kind code	B2
Filing date	Apr 25, 2013
Priority date	Apr 25, 2012
Publication date	May 19, 2020
Grant date	May 19, 2020

Abstract

Provided herein relates to compositions and methods for lubrication of a surface. The surface amenable to the compositions and methods described herein can be a non-biological surface, a biological surface, or a combination thereof. In some embodiments, the composition comprising a phospholipid-coated silk microsphere can be used for lubrication of a surface. In some embodiments, the composition comprising a phospholipid-coated silk microsphere can be used for joint lubrication, e.g., for treatment of joint disorders such as arthritis.

First claim

What is claimed is:

1. A lubricated microsphere comprising:
a silk fibroin microsphere comprising
one or more pores having a pore size range of 1 nm to 100 μm,
wherein the silk fibroin is free of lipid; and

a phospholipid coating on a surface of the silk fibroin microsphere,
wherein when the lubricated microsphere is under a cyclic shear loading pressure of at least 0.08 MPa for at least a week, the lubricated microsphere resist degradation, and
wherein the lubricated microsphere is characterized by a static friction coefficient of less than 0.1, as determined by a friction test against a silica surface.

2. The lubricated microsphere of claim 1 , wherein the lubricated microsphere has a width dimension of about 1 μm to about 100 μm.

3. The lubricated microsphere of claim 1 , wherein the lubricated microsphere has a width dimension of at least about 3 μm or higher.

4. The lubricated microsphere of claim 1 , wherein an amount of the phospholipid coating present on the lubricated microsphere ranges from about 0.01 wt % to about 10 wt %.

5. The lubricated microsphere of claim 1 , wherein the phospholipid coating comprises one or more phospholipids.

6. The lubricated microsphere of claim 1 , wherein the lubricated microsphere further comprises an additive or active agent.

7. The lubricated microsphere of claim 6 , wherein the additive or active agent is present in and/or on the phospholipid coating, the silk microsphere, or a combination thereof.

8. The lubricated microsphere of claim 1 , wherein the lubricated microsphere is substantially spherical.

9. The lubricated microsphere of claim 1 , wherein the lubricated microsphere is formulated for use in a mammalian subject.

10. The lubricated microsphere of claim 9 , wherein the lubricated microsphere is formulated for use as a joint lubricant.

11. A method comprising placing between a first biological surface and a second biological surface a lubricated microsphere of claim 1 , thereby reducing friction between the first biological surface and the second biological surface.

12. A method of treating arthritis in a subject comprising placing between two joint surfaces in the subject a lubricated microsphere of claim 1 , thereby reducing friction between the two joint surfaces.

13. A method of making a lubricated microsphere comprising:
sonicating a mixture comprising
silk fibroin microspheres,
wherein the silk fibroin microspheres are free of lipid and

a lipid composition, whereby the sonicating forms a suspension comprising lubricated microspheres that comprise the lipid composition coating a surface of the silk fibroin microsphere, wherein each silk fibroin microsphere of the lubricated microspheres comprises a pore having a pore size range of 1 nm to 100 μm, and

wherein when the lubricated microsphere is under a cyclic shear loading pressure of at least 0.08 MPa for at least a week, the lubricated microsphere resists degradation.

14. The method of claim 13 , wherein the concentration of the lipid composition in the mixture is about 5 wt % to about 50 wt %, or about 10 wt % to about 30 wt %.

15. The method of claim 13 , wherein the concentration of the lipid composition in the mixture ranges from about 0.05% wt % to about 10 wt %.

16. A method of making a lubricated microsphere comprising a silk microsphere substantially free of lipid and a phospholipid coating lubricating a surface of the silk microsphere, the method comprising:
a. sonicating a mixture comprising a silk fibroin solution and a PVA solution wherein the silk fibroin solution is free of lipid;
b. lyophilizing the mixture;
c. dissolving the lyophilized mixture in an aqueous solution;
d. removing at least a portion of the PVA, thereby forming a silk microsphere; and
e. sonicating the silk microsphere with a hydrated lipid composition, thereby forming a lubricated microsphere, wherein each silk fibroin microsphere of the lubricated microspheres comprises a pore having a pore size range of 1 nm to 100 μm.

17. The method of claim 16 , wherein the PVA solution has a concentration of about 1 wt % to about 10 wt %.

18. The method of claim 13 , further comprising separating smaller-sized lubricated microspheres from larger-sized lubricated microspheres.

19. The method of claim 13 , wherein the lipid composition comprises one or more phospholipids.

20. The method of claim 13 , wherein the silk fibroin present in the silk fibroin microspheres is in an amount of at least 5%.

21. The method of claim 13 , wherein the silk fibroin microspheres further comprise an additive or active agent.

22. A lubricated microsphere produced by the method of claim 13 .

23. The method of claim 13 , further comprising a step of lyophilizing at least a portion of the suspension.

24. The method of claim 16 , where the volume ratio of the silk fibroin solution to the PVA solution is about 1:1 to about 10:1.

Assignees

• Tufts College
• The Administrators Of The Tulane Educational Fund
• Tulane Educat Fund Inc

Inventors

• Kaplan David L
• Wang Xiaoqin
• John Vijay
• Pesika Noshir
• Zheng Rubo

Classifications

• A61L27/54

  Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} · CPC title

• A61K9/1617

  Organic compounds, e.g. phospholipids, fats · CPC title

• A61L2300/622

  Microcapsules · CPC title

• A61K47/42 Primary

  Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34) · CPC title

• A61L2400/10

  Materials for lubricating medical devices · CPC title