Antibiofouling catheter and related systems

Abstract

A catheter system includes a catheter adapter (12), which includes a distal end and a proximal end. The catheter system includes a catheter (18) extending from the distal end of the catheter adapter. The catheter includes an outer surface (20) having an active area (22) and a passive area (24) proximate the active area. The active area includes a microbiocidal agent. The passive area is more hydrophilic than the active area to facilitate bacterial adhesion at the active area compared to the passive area. In further detail, the passive area may be superhydrophilic. The passive area may be superhydrophobic and the active area may not be superhydrophobic to facilitate bacterial adhesion at the active area compared to the passive area.

Description

ANTIBIOFOULING CATHETER AND RELATED SYSTEMS AND METHODSBACKGROUND

[0001] Indwelling medical devices include medical devices which are susceptible to bacterial colonization and infection due to prolonged contact with blood or body fluids. Examples of indwelling medical devices include, but are not limited to, catheters, such as central venous catheters (CVCs) and peripherally inserted central catheters (PICCs), urinary catheters, dialysis catheters, as well as auxiliary equipment and tubing that contacts blood, such as blood infusion equipment, plasma collection equipment, dialysis equipment, etc.

[0002] Catheters are life saving devices that have become a standard of care. Catheter-related bloodstream infection (CRB SI) and central line-associated bloodstream infection (CLABSI) are caused by the colonization of microorganisms in patients with intravascular catheters and access devices. These infections are an important cause of illness and excess medical costs, as approximately 250,000 - 400,000 cases of central venous catheter (CVC) associated bloodstream infections occur annually in U.S. hospitals. In addition to the monetary costs, these infections are associated with anywhere from 20,000 to 100,000 deaths each year. Despite guidelines to help reduce healthcare associated infections (HAIs), catheter-related bloodstream infections continue to plague our healthcare system.

[0003] Multiple approaches are utilized to mitigate the occurrence of these infections - namely proper insertion site cleaning, good catheter placement practice, and use of antimicrobial agents in or on the catheter tubing to suppress microbial growth. To provide antimicrobial properties, antimicrobial agents have been immobilized into the catheter matrix or coated onto the catheter surface. These catheters, however, have given less than satisfactory results. Accordingly, there is a need in the art for catheters having improved antimicrobial capabilities.

[0004] The subject matter claimed herein is not limited to embodiments that solve any disadvantages or that operate only in environments such as those described above. Rather, this background is only provided to illustrate one example technology area where some implementations described herein may be practiced.SUMMARY

[0005] The present disclosure relates generally to an antibiofouling catheter and related systems and methods. In some embodiments, a catheter system may include a catheter adapter, which may include a distal end and a proximal end. In some embodiments, the catheter system may include a catheter, which may extend from the distal end of the catheter adapter. In some embodiments, the catheter system may be peripheral intravenous, central venous, midline, or arterial catheter system. In some embodiments, the catheter system may be a urinary or dialysis catheter system or another suitable type of catheter system.

[0006] In some embodiments, the catheter may include an outer surface having an active area and a passive area proximate the active area. In some embodiments, the catheter may include an inner surface forming an inner lumen, and the active area and the passive area may extend from the outer surface to the inner surface of the catheter.

[0007] In some embodiments, the passive area may be more hydrophilic than the active area to facilitate bacterial adhesion at the active area compared to the passive area. In some embodiments, the passive area may be superhydrophilic such that a water contact angle is between 0 degrees and 10 degrees. In some embodiments, the passive area may include a superhydrophilic coating. In some embodiments, the superhydrophilic coating may include a hydrogel.

[0008] In some embodiments, the passive area may have lower friction than the active area.

[0009] In some embodiments, the active area may include a microbioci dal agent. Non-limiting examples of the microbiocidal agent include a nitric oxide donor, silver, and chlorhexidine.

[0010] In some embodiments, the active area may be proximal to the passive area and configured to align with an insertion site of the catheter when the catheter is indwelling in a blood vessel of a patient. In some embodiments, the catheter may include a distal tip, and the passive area may extend to the distal tip.

[0011] In some embodiments, the outer surface of the catheter may include multiple active areas and multiple passive areas. In some embodiments, the active areas and the passive areas may alternate along a length of the catheter. In some embodiments, each of the active areas proximal to the distal tip and each of the passive areas proximal to the distal tip may be cylindrical.

[0012] In some embodiments, the active area and / or the passive area may include a surface topography having multiple features that are spaced apart and have at least one microscale dimension.

[0013] In some embodiments, the passive area may be superhydrophobic and the active area may not be superhydrophobic to facilitate bacterial adhesion at the active area compared to the passive area. In some embodiments, the passive area may include a superhydrophobic coating.

[0014] It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory and are not restrictive of the invention, as claimed. It should be understood that the various embodiments are not limited to the arrangements and instrumentality shown in the drawings. It should also be understood that the embodiments may be combined, or that other embodiments may be utilized and that structural changes, unless so claimed, may be made without departing from the scope of the various embodiments of the present invention. The following detailed description is, therefore, not to be taken in a limiting sense.BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0015] Example embodiments will be described and explained with additional specificity and detail through the use of the accompanying drawings in which:

[0016] Figure 1A is an upper perspective view of an example catheter system, illustrating an example catheter having an active area and a passive area, according to some embodiments;

[0017] Figure IB is an upper perspective view of the catheter of Figure 1A, according to some embodiments;

[0018] Figure 1C is a cross-sectional view of the catheter of Figure 1A extending from an example catheter adapter of the catheter system, according to some embodiments;

[0019] Figure 2A is an upper perspective view of the catheter system, illustrating the catheter having multiple active areas and multiple passive areas, according to some embodiments;

[0020] Figure 2B is an upper perspective view of the catheter of Figure 2A, according to some embodiments;

[0021] Figure 2C is a cross-sectional view of the catheter of Figure 2A extending from the catheter adapter of the catheter system, according to some embodiments;

[0022] Figure 3A is an upper perspective view of an example surface topography having multiple features and an example superhydrophilic coating, according to some embodiments; and

[0023] Figure 3B is an upper perspective view of the surface topography having multiple features and an example superhydrophobic coating, according to some embodiments.DESCRIPTION OF EMBODIMENTS

[0024] Referring now to Figures 1A-1B, in some embodiments, a catheter system 10 may include a catheter adapter 12, which may include a distal end 14 and a proximal end 16. In some embodiments, a lumen may extend between the distal end 14 and the proximal end 16. In some embodiments, the catheter system 10 may include a catheter 18, which may extend from the distal end 14 of the catheter adapter 12. In some embodiments, the catheter 18 may be tubular.

[0025] Biofilms, which are surface-associated bacterial colonies, pose a significant concern for indwelling catheters and in various diseases. They represent the predominant form of bacterial existence in nature, found on both biological and non-biological surfaces. The initial phase of biofilm development involves surface adhesion, where a free-floating bacterium attaches to a surface. This adhesion is considered essential for the formation of biofilms and often becomes permanent after a period of time. Following adhesion, surface colonization occurs as the attached bacteria multiply and spread across the surface.

[0026] In some embodiments, the catheter 18 may include an outer surface 20 having an active area 22 and a passive area 24 proximate the active area 22. In some embodiments, the outer surface 20 corresponds to outer-most surface of the catheter 18 configured to contact blood when the catheter 18 is inserted into a blood vessel of a patient. In some embodiments, the passive area 24 proximate the active area 22 may facilitate preferential attachment of biofilm to the active area 22 such that the biofilm can then be destroyed in a controlled manner. In further detail, the passive area 24 may be more hydrophilic than the active area 22 to facilitate bacterial adhesion at the active area 22 compared to the passive area 24. In some embodiments, the passive area 24 may be superhydrophilic.

[0027] In some embodiments, the passive area 24 that is hydrophilic or superhydrophilic nature may facilitate formation of a hydration layer on the passive area 24 that prevents direct contact between the passive area 24 and bacteria. Hydrophilic surfaces, and to a greater extent superhydrophilic surfaces, have a high affinity for water, leading to formation of a stable, tightly bound layer of water molecules. Due to the passive area 24 being hydrophilic or superhydrophilic, it is difficult for bacteria to displace the strongly bound water molecules and adhere to the passive area 24.

[0028] Bacteria have surface sensing mechanisms to search for favorable environments for cell adhesion. When the passive area 24 is blocked by the hydration layer, bacteria may preferentially choose to adhere to the active area 22, which may be proximate the passive area 24. In some embodiments, the active area 22 may include a microbiocidal agent such that the bacteria adhered to the active area 22 may be destroyed. Thus, in some embodiments, the catheter system 10 may provide a two-prong approach to infection prevention: 1) disrupting the mechanism of microbial attachment at the passive area 24 via the hydration layer, and 2) disinfecting attached microbes using biocides.

[0029] In some embodiments, the microbiocidal agent may include a nitric oxide donor. In some embodiments, the microbiocidal agent may include silver sulfadiazine or another suitable silver-containing compound. In some embodiments, the microbiocidal agent may include chlorhexidine acetate, chlorhexidine gluconate (CHG), or another suitable chlorhexidine- containing compound. Other non-limiting examples of suitable microbiocidal agents may include polyhexamethylene biguanide (PHMB), conjugated oligomers (COEs), and dendritic polyethylene imine (PEI) modified not to be toxic to animal cells.

[0030] In some embodiments, the microbiocidal agent may be included in the active area 22 according to any suitable method known in the art. In some embodiments, the microbiocidal agent may be a coating. In some embodiments, the microbiocidal agent may be incorporated into a polymer matrix of a material of a wall forming the catheter 18. In some embodiments, the microbiocidal agent may be impregnated into the material of the wall during manufacturing and released over time. In some embodiments, the passive area 24 may not include the microbiocidal agents or any microbiocidal agents.

[0031] In some embodiments, the microbiocidal agent may act according to one or more of the following: 1) inhibition of cell wall synthesis, 2) inhibition of protein synthesis, 3) inhibition of nucleic acid synthesis, 4) affects cell membrane sterols, and 5) inhibition of unique metabolic steps. Non-limiting examples of microbiocidal agents that inhibit cell wall synthesis include chlorhexidine, penicillin, and vancomycin. Non-limiting examples of microbiocidal agents that inhibit protein synthesis include silver ions, nitric oxide, and tetracyclines such as minocycline. Non-limiting examples of microbiocidal agents that inhibit nucleic acid synthesis include sparfloxacin, quinolones, nitric oxide, and rifampin. Non-limiting examples of microbiocidal agents that affect cell membrane sterols include silver ions, triclosan, antimicrobial peptides, and antifungal agents such as amphotericin. Non-limiting examples of microbiocidal agents that inhibit unique metabolic steps include nitrofuran, triclosan, bacteriophages, and sulfonamide. In some embodiments, the microbiocidal agent may eliminate bacteria after they have attached to a surface and / or may not prevent adhesion of the bacteria to the surface.

[0032] In some embodiments, the passive area 24 may have lower friction than the active area22, which may further facilitate bacteria binding to the active area 22 instead of the passive area24. The passive area 24 being a low friction surface or having lower friction than the active area22 can reduce mechanical interlocking or attachment of bacteria, especially in a blood vessel where there is flow, and may allow bacteria to slide over the passive area 24 more easily. In some cases, the bacteria may slide to the adjacent active area 22. In some embodiments, the passive area 24 may be a low friction surface and / or the active area 22 may be a high friction surface. In some embodiments, the hydrophilic or superhydrophilic characteristics of the passive area 24 may cause the passive area 24 to be low friction due to the hydration layer.

[0033] In some embodiments, the passive area 24 may be superhydrophilic such that a water contact angle is between 0 degrees and 10 degrees or between 0 degrees and 5 degrees, which may facilitate bacterial adhesion at the active area 22 compared to the passive area 24. In some embodiments, the passive area 24 may include a superhydrophilic coating. In some embodiments, the superhydrophilic coating may include a hydrogel. In some embodiments, the hydrogel may include a hyaluronic acid-based hydrogel, polyethylene glycol-based hydrogel, polyvinylpyrrolidone-based hydrogel, poly(2-hydroxyethyl methacrylate) (pHEMA), or another suitable hydrogel.

[0034] In some embodiments, the passive area 24 may include a functionalized or smart surface configured to reduce adhesion of bacteria to the passive area 24. In some embodiments, the passive area 24 may include more than one type of surface or mechanism to reduce adhesion of bacteria. For example, the passive area 24 may be superhydrophilic and may include a surface topography having multiple features, which may decrease adhesion of bacteria to the passive area 24. In some embodiments, the multiple features each have at least one microscale dimension and at least one neighboring feature having a substantially different geometry In some embodiments, the multiple features may be attached to or projected into a base article, such as, for example, the catheter 18. As used in the present disclosure, the term “microscale” includes micron size orsmaller features, thus including microscale and nanoscale. Non-limiting examples of surface topographies are described further in U.S. Patent No. 7,650,848, filed December 5, 2006, entitled“SURFACE TOPOGRAPHIES FOR NON-TOXIC BIO ADHESION CONTROL,” U.S. Patent No. 9,016,221, filed August 31, 2009, entitled “SURFACE TOPOGRAPHIES FOR NON-TOXIC BIOADHESION CONTROL,” and U.S. Patent No. 10,150,245, filed February 1, 2010, entitled “METHOD OF PATTERNING A SURFACE AND ARTICLES COMPRISING THE SAME,” which are herein incorporated by reference in their entirety. In some embodiments, the active area 22 may also include the surface topography, which may decrease adhesion of bacteria to the active area 22. In some embodiments, the surface topography may be formed through one or more techniques, including, but not limited to, laser ablation, lithography, spray coating, sol-gel, and electrospinning.

[0035] In some embodiments, the multiple features of the surface topography may be spaced and / or arranged in groupings or patterns, which may include repeat units. In some embodiments, the spaced features within a grouping may be spaced apart at an average distance of 1 nanometer to about 500 micrometers, for example. In some embodiments, the multiple features and / or groupings of features may be arranged within respect to one another to define a tortuous pathway. In some embodiments, the multiple features neighboring each other may have different geometries and at least one microscale dimension. In some embodiments, the active area 22 may be uniform and / or may not include the topography having the multiple features such that bacterial adhesion at the active area 22 is greater compared to the passive area 24.

[0036] In some embodiments, the active area 22 may not be hydrophilic or superhydrophilic such that bacterial adhesion at the active area 22 is greater compared to the passive area 24. In some embodiments, the active area 22 may include polyurethane, polyvinyl chloride, or anothersuitable plastic. In some embodiments, the active area 22 may be polytetraflouroethylene or another suitable material. In some embodiments, the active area 22 may not include a coating. In some embodiments, when bacterial adhesion is concentrated at the active area 22, with bacteria adhering to the active area 22 more than the passive area 24, the active area 22 may include or act as a sensor to provide early detection of infection before sepsis develops. In some embodiments, the active area 22 the active area 22 may include a sensor such as a pH or lactate sensor, which may facilitate monitoring onset of one or more of infection, thrombus, or sepsis to avoid further complications.

[0037] In some embodiments, the active area 22 may be proximal to the passive area 24 and configured to align with an insertion site of the catheter 18 when the catheter 18 is indwelling in the blood vessel of the patient. In these and other embodiments, a distal end of the active area 22 may be disposed about half-way between the distal end 14 of the catheter adapter 12 and a distal tip 26 of the catheter 18. In some embodiments, the active area 22 may extend proximally to the distal end 14 of the catheter adapter 12, which may facilitate bacteria moving away from the patient. Providing the active area 22 or a zone of disinfection at or near the insertion site of the catheter 18 may help prevent bacteria from migrating further quickly and may help provide a controlled zone of attack against infection rather than uncontrolled treatment of an entire catheter.

[0038] In some embodiments, the catheter 18 may include the distal tip 26 that may be proximate an aperture providing access to an inner lumen of the catheter 18, and the aperture may have a tendency to accumulate bacteria in a way that occludes the catheter 18. In some embodiments, the passive area 24 may extend to the distal tip 26, which may reduce a risk of occlusion of the catheter 18 at the aperture.

[0039] Referring now to Figure 1C, in some embodiments, the active area 22 and the passive area 24 may extend from the outer surface 20 to an inner surface 28 of the catheter 18. In these embodiments, the active area 22 and the passive area 24 may reduce biofouling within the catheter 18. In some embodiments, the inner surface 28 may form an inner lumen 30 of the catheter 18, which may be in fluid communication with the lumen of the catheter adapter 12.

[0040] Referring now to Figures 2A-2B, in some embodiments, the outer surface 20 of the catheter 18 may include multiple active areas 22 and multiple passive areas 24. In some embodiments, the active areas 22 and the passive areas 24 may alternate along a length of the catheter 18, which may facilitate movement of bacteria from the passive areas 24 to the active areas 22 nearby. In some embodiments, due to weak adhesion to the passive areas 24, bacterial flow may be propelled forward and eventually reach one of the active areas 22 and get neutralized. In some embodiments, the active areas 22 and the passive areas 24 may alternate along an entire length of the catheter 18 from the distal tip 26 to the distal end 14 of the catheter adapter 12. In some embodiments, a particular passive area 24 may be flanked on both sides by a first particular active area and a second particular active area.

[0041] In some embodiments, each of the active areas 22 proximal to the distal tip 26 and each of the passive areas 24 proximal to the distal tip 26 may be cylindrical, which may provide annular protection from bacteria. In some embodiments, the distal tip 26 may taper inwardly in a distal direction, which may facilitate insertion of the distal tip 26 through skin and the blood vessel of the patient.

[0042] Referring now to Figure 2C, in some embodiments, the active areas 22 and the passive areas 24 may extend from the outer surface 20 to the inner surface 28 of the catheter 18. In these embodiments, the active areas 22 and the passive areas 24 may reduce biofouling within thecatheter 18. In some embodiments, the inner surface 28 may form the inner lumen 30 of the catheter 18, which may be in fluid communication with the lumen of the catheter adapter 12.

[0043] Referring now to Figure 3A, a schematic diagram illustrates a surface topography 32 having multiple features 34 and the hydration layer on top of the surface topography 32, according to some embodiments. In some embodiments, bacteria 36 may be prevented from adhering to the passive area 24 due to the surface topography 32 working in conjunction with a superhydrophilic coating.

[0044] Referring now to Figure 3B, a schematic diagram illustrates the surface topography 32 having the multiple features 34, according to some embodiments. In some embodiments, the passive area 24 may be superhydrophobic and the active area may not be superhydrophobic to facilitate bacterial adhesion at the active area compared to the passive area 24. In some embodiments, the passive area 24 may include a superhydrophobic coating, which may exhibit a contact angle with water greater than 150 degrees. In some embodiments, the superhydrophobic coating may include one or more of silver nanoparticles, silver, copper, titanium dioxide, zinc oxide, silica, or another suitable material.

[0045] In some embodiments, the passive area 24 that is superhydrophobic may provide antibiofouling properties to the catheter 18 due to high water repellency characterized by very high contact angles (greater than 150 degrees) between water droplets and the passive area 24. Thus, a rolling-off effect of water droplets on the passive area 24 that is superhydrophobic can physically remove bacteria. Moreover, in some embodiments, the passive area 24 that is superhydrophobic may demonstrate reduced surface attachment due to a cushion of air between the passive area 24 that is superhydrophobic and bacteria in a liquid medium. Additionally, the same properties that repel water from the passive area 24 that is hydrophobic prevent accumulation of nutrients andorganic matter on the passive area 24. The lack of nutrients and organic matter may prevent bacteria from colonizing on the passive area 24 since they rely on the nutrients and the organic matter for initial growth and biofdm formation. In some instances, the very high contact angles and low surface energy of the passive area 24 may increase a thermodynamic energy barrier for bacterial adhesion, and it becomes energetically unfavorable for bacteria to make a transition from a suspended state in liquid to an adhered state on the passive area 24. In some embodiments, the bacteria 36 may be prevented from adhering to the passive area 24 due to the surface topography 32 working in conjunction with the superhydrophobic coating.

[0046] Reference throughout this specification to “one embodiment,” “certain embodiments,” “one or more embodiments” or “an embodiment” means that a particular feature, structure, material, or characteristic described in connection with the embodiment is included in at least one embodiment of the invention. Thus, the appearances of the phrases such as “in one or more embodiments,” “in certain embodiments,” “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily referring to the same embodiment of the invention. Furthermore, the particular features, structures, materials, or characteristics may be combined in any suitable manner in one or more embodiments.

[0047] Although the invention herein has been described with reference to particular embodiments, it is to be understood that these embodiments are merely illustrative of the principles and applications of the present invention. It will be apparent to those skilled in the art that various modifications and variations can be made to the method and apparatus of the present invention without departing from the spirit and scope of the invention. Thus, it is intended that the present invention include modifications and variations that are within the scope of the appended claims and their equivalents.

Claims

CLAIMS1. A catheter system, comprising: a catheter adapter comprising a distal end and a proximal end; and a catheter extending from the distal end of the catheter adapter, wherein the catheter comprises an outer surface having an active area and a passive area proximate the active area, wherein the passive area is more hydrophilic than the active area to facilitate bacterial adhesion at the active area compared to the passive area.

2. The catheter system of claim 1, wherein the passive area has lower friction than the active area.

3. The catheter system of claim 1, wherein the passive area is superhydrophilic such that a water contact angle is between 0 degrees and 10 degrees.

4. The catheter system of claim 3, wherein the passive area comprises a superhydrophilic coating.

5. The catheter system of claim 4, wherein the superhydrophilic coating comprises a hydrogel.

6. The catheter system of claim 1, wherein the active area comprises a microbiocidal agent.

7. The catheter system of claim 6, wherein the microbiocidal agent comprises a nitric oxide donor, silver, or chlorhexidine.

8. The catheter system of claim 1, wherein the active area comprises polyurethane.

9. The catheter system of claim 1 , wherein the active area is proximal to the passive area and configured to align with an insertion site of the catheter when the catheter is indwelling in a blood vessel of a patient.

10. The catheter system of claim 1, wherein the catheter comprises a distal tip, wherein the passive area extends to the distal tip.

11. The catheter system of claim 1, wherein the outer surface of the catheter comprises a plurality of active areas and a plurality of passive areas, wherein the plurality of active areas and the plurality of passive areas alternate along a length of the catheter.

12. The catheter system of claim 11, wherein each of the plurality of active areas proximal to the distal tip and each of the plurality of passive areas proximal to the distal tip are cylindrical.

13. The catheter system of claim 1, wherein the passive area comprises a surface topography having plurality of features that are spaced apart and have at least one microscale dimension.

14. A catheter system, comprising: a catheter adapter comprising a distal end and a proximal end; and a catheter extending from the distal end of the catheter adapter, wherein the catheter comprises an outer surface having an active area and a passive area proximate the active area, wherein the passive area is superhydrophobic and the active area is not superhydrophobic to facilitate bacterial adhesion at the active area compared to the passive area.

15. The catheter system of claim 14, wherein the passive area has lower friction than the active area.

16. The catheter system of claim 14, wherein the passive area comprises a superhydrophobic coating.

17. The catheter system of claim 14, wherein the active area comprises a microbiocidal agent.

18. The catheter system of claim 14, wherein the catheter further comprises an inner surface forming an inner lumen, wherein the active area and the passive area extend from the outer surface to the inner surface of the catheter.

19. The catheter system of claim 14, wherein the outer surface of the catheter comprises a plurality of active areas and a plurality of passive areas, wherein the plurality of active areas and the plurality of passive areas alternate along a length of the catheter.

20. The catheter system of claim 14, wherein the passive area comprises a surface topography having plurality of features that are spaced apart and have at least one microscale dimension.

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