Incorporation of particulate ceragenins in polymers
View Patent ↗A composite that includes a polymeric material having a void structure and particulate ceragenin material (i.e., ceragenin particles) associated with the void structure. The average particle size of the ceragenin particles in the composite is in a range from 5 nm to 20 μm, 50 nm to 10 μm, 100 nm to 5 μm, or 1 μm to 10 μm. The composite has a high loading of ceragenin particles (e.g., about 10% to about 25%, by weight). The composite has good polymer stability, the ability to release ceragenins from the ceragenin particles disposed in the composite over a sustained period of time at a characteristic elution rate, and the ability to kill large numbers of bacteria and other susceptible microbes over the sustained period of time.
1. A composite, comprising:
a polymeric material with steroidal particles dispersed therein,
wherein the steroidal particles consist essentially of at least one ceragenin compound having a structure as in Formula (I):
where,
each of m, n, p, and q is independently 0 or 1, and
at least three of R 1 through R 4 , R 6 , R 7 , R 11 , R 12 , R 15 , R 16 , R 17 , and R 18 include a heteroatom selected from O and N and at least one alkyl or aryl group attached to the heteroatom,
wherein the steroidal particles are disposed in a void structure in the polymeric material, and
wherein the steroidal particles comprise 1 wt % to 25 wt % of the composite and have an average particle size in a range from 5 nm to 40 μm.
2. The composite of claim 1 , wherein the void structure is formed by the steroidal particles.
3. The composite of claim 1 , wherein the void structure includes voids having a size in a range from 5 nm to 40 μm.
4. The composite 3 , wherein the void size is substantially uniform.
5. The composite of claim 1 , wherein the void structure is water accessible such that the at least one ceragenin compound can be eluted out of the composite.
6. The composite of claim 1 , wherein the polymeric material is selected from the group consisting of a silicone polymer, a vinyl polymer, a urethane polymer, a methacrylate polymer, a polyester, and combinations thereof.
7. A kit for use in making the composite of claim 1 , comprising:
steroidal particles having an average particle size in a range from 5 nm to 40 μm and consisting essentially of the at least one ceragenin compound;
a dispersant configured to disperse the steroidal particles, wherein the steroidal particles are substantially insoluble in the at least one dispersant;
a polymerizable material; and
a protocol for preparing a composite that includes the steroidal particles, the dispersant, and the polymerizable material, and so that the steroidal particles comprise 1 wt % to 25 wt % of the composite.
8. The kit of claim 7 , wherein the dispersant is a non-polar organic solvent.
9. The kit of claim 7 , wherein the polymerizable material is selected from the group consisting of a monomer, a precursor, a prepolymer, an oligomer, or a polymer of a silicone, a vinyl, a urethane, a methacrylate, a polyester, and combinations thereof.
10. The kit of claim 7 , wherein the average particle size of the steroidal particles is in a range from 5 nm to 20 μm.
11. A composite made from the kit of claim 7 , wherein the composite includes the steroidal particles dispersed in a polymer made by polymerization of the polymerizable material.
12. A method of preparing the composite of claim 1 , comprising:
dispersing the steroidal particles in a polymerizable material to form a polymerizable mixture; and
polymerizing the polymerizable material to yield composite having the steroidal particles dispersed therein.
13. The method of claim 12 , further comprising:
providing a ceragenin mixture that includes the steroidal particles dispersed in a dispersant; and
dispersing the ceragenin mixture in the polymerizable material to form the polymerizable mixture.
14. The method of claim 13 , wherein the dispersant is a non-polar organic solvent.
15. The method of claim 14 , wherein the non-polar organic solvent is selected from the group consisting of naphtha, xylenes, pentane, cyclopentane, hexanes, cyclohexane, benzene, toluene, dioxane, chloroform, diethyl ether, dichloromethane, and combinations thereof.
16. The method of claim 14 , wherein the dispersant is miscible in the polymerizable material.
17. The method of claim 12 , wherein the polymerizable material is selected from the group consisting of a monomer, a precursor, a prepolymer, an oligomer, or a polymer of a silicone, a vinyl, a urethane, a methacrylate, a polyester, and combinations thereof.
18. The method of claim 12 , further comprising applying the mixture to a substrate prior to the polymerizing to yield a substrate coated with the composite.
19. The method of claim 12 , wherein the composite includes 1% weight/weight (“wt %”) to 25 wt % steroidal particles.
20. The method of claim 12 , wherein the at least one ceragenin compound has a number of cationic groups attached to the sterol backbone.