Long-term indwelling medical devices containing slow-releasing antimicrobial agents and having a surfactant surface
A medical device for long-term implantation is provided, as well as a method of making the same and a method of treatment using the same. The medical device comprises (1) a reservoir including (a) a polymer matrix and (b) an antimicrobial agent disposed within the polymer matrix, wherein the reservoir is adapted for long-term release of the antimicrobial agent from the polymer matrix; and (2) a surfactant region disposed over the reservoir at an outer surface of the device.
1. A medical device comprising:
a reservoir comprising (a) a polymer matrix and (b) an antimicrobial agent disposed within said polymer matrix, said reservoir adapted for long-term release of said antimicrobial agent from said polymer matrix; and
a surfactant region comprising a surfactant, said surfactant region disposed over said reservoir at an outer surface of said medical device;
wherein said reservoir is not a coating layer on said medical device; and
wherein said medical device is a urine contacting device adapted for long-term implantation within the body of a patient.
2. The medical device of claim 1 , wherein said surfactant region comprises a biosurfactant.
3. The medical device of claim 2 , wherein said biosurfactant is selected from glycolipids, lipopeptides, depsipeptides, phospholipids, substituted fatty acids, and lipopolysaccharides.
4. The medical device of claim 2 , wherein said biosurfactant is selected from surlactin, surfactin, visconsin and rhamnolipids.
5. The medical device of claim 1 , wherein said surfactant is a surfactant polymer.
6. The medical device of claim 5 , wherein said surfactant polymer is a surfactant polymer having a poly(vinyl amine) backbone and having hydrophilic poly(ethylene oxide) and hydrophobic hexanal side chains.
7. The medical device of claim 1 , wherein said surfactant is linked to said outer surface by one or more interactions selected from hydrophobic interactions, ionic interactions and covalent interactions.
8. The medical device of claim 1 , wherein said medical device is selected from a ureteral stent and a urethra catheter.
9. The medical device of claim 1 , wherein said antimicrobial agent is selected from triclosan, chlorhexidine, silver sulfadiazine, silver ions, benzalkonium chloride and zinc pyrithione.
10. The medical device of claim 1 , wherein said antimicrobial agent is a broad-spectrum antibiotic.
11. The medical device of claim 1 , wherein said antimicrobial agent is an antiseptic agent.
12. The medical device of claim 11 , wherein said antiseptic agent is iodine.
13. The medical device of claim 1 , wherein said polymer matrix comprises a polymer selected from an ethylene-vinyl acetate copolymer and a polyurethane.
14. A method of treatment comprising:
providing the urine contacting medical device of claim 1 ; and
implanting said urine contacting medical device within the body of a patient for a period of at least three months.
15. The method of claim 14 , wherein said surfactant is a biosurfactant.
16. The method of claim 14 , wherein said surfactant is a surfactant polymer.
17. The method of claim 14 , wherein said polymer matrix comprises a polymer selected from an ethylene-vinyl acetate copolymer and a polyurethane.
18. A method of constructing the medical device of claim 1 , comprising:
forming said reservoir; and
providing a surfactant region comprising a surfactant over said reservoir at an outer surface of said medical device.
19. The method of claim 18 , wherein said antimicrobial agent is disposed within said polymer matrix at the time of formation of said polymer matrix.
20. The method of claim 19 , wherein said antimicrobial agent is co-cast with said polymer matrix.
21. The method of claim 19 , wherein said antimicrobial agent is co-extruded with said polymer matrix.
22. The method of claim 18 , wherein said antimicrobial agent is provided within said polymer matrix by imbibing said antimicrobial agent into said polymer matrix.
23. The method of claim 18 , wherein said surfactant is a biosurfactant.
24. The method of claim 18 , wherein said surfactant is a surfactant polymer.
25. The method of claim 18 , wherein said surfactant is covalently linked at said outer surface of said device.
26. The method of claim 18 , wherein said antimicrobial agent is selected from triclosan, chlorhexidine, silver sulfadiazine, silver ions, benzalkonium chloride and zinc pyrithione.
27. The medical device of claim 1 , wherein said reservoir is in the form of a tubular medical device component, and wherein said surfactant region is provided in the form of a layer disposed over said reservoir.
28. The medical device of claim 27 , wherein said tubular medical device component is selected from a stent body and a catheter tube.