Hospital-acquired infections (HAIs) are a major area of concern for providers, payers, and patients alike. These infections play a significant role in the estimated 44,000 to 98,000 preventable health care-associated deaths in America each year. Plus, with new regulatory mandates for Medicare and Medicaid prohibiting federal payments to states for treatment of certain hospital-acquired conditions, there is increasing pressure on hospitals to find new and better solutions for prevention. Silicone elastomers and adhesives preloaded with anti-infective additives for medical devices provide an example of the type of materials innovation that can help advance health care in this present environment.
Many largely preventable HAIs develop due to catheterization or at a patient’s surgical incision site. According to the Centers for Disease Control and Prevention, in the United States, 92,000 central line-associated bloodstream infections occur each year, increasing health care costs by $18,222 on average. Also, about 450,000 catheter-associated urinary tract infections occur each year, increasing costs by $935 on average. Surgical site infections are the second most common source of HAIs in US hospitals (290,000 per year) and account for the greatest additional health care cost, between $3.5 and $10 billion per year, reports the California Department of Public Health. As the population ages and chronic illnesses become more prevalent, the rates of these types of infections are expected to increase.
Biofilms are complex communities of microbes, such as bacteria and fungi, that product and excrete a protective material called extracellular polymeric substance, a thick fluid comprised mainly of sugars and protein. Biofilms are mainly found on surfaces. Medical device surfaces, such as the inside or outside of a catheter, are more likely to be colonized as they are foreign materials that provide a barrier protecting one side of the microbial community from the body’s own infection-fighting immune system. Once established, biofilm infections are very difficult to eradicate, frequently requiring removal of the infected device. Preventing the initial formation of biofilm through the use of antimicrobials or other counter-biofilm functionality is preferable.
To help avoid infections, particularly microbial biofilms— the most prevalent form of medical device-related infection— many device manufacturers use antimicrobials, such as antibiotics, in their products. Historically, these actives have been incorporated via coating or impregnating the device components. Examples include coating catheters with a silver-based antimicrobial agent and impregnating antibiotics into silicone rubber parts, such as hydrocephalus shunts, using a solventbased carrier. However, these approaches have drawbacks, including the cost of secondary operations, risks of inconsistent application or premature dissipation, wearing-off (delamination), dimensional issues, and a limited ability to fine-tune the rate of release of the active agent.
Bulk Loading of Actives: A New Strategy
A promising new technique is bulk loading the antimicrobial, antibiotic, or other active into a silicone elastomer prior to vulcanization (curing) and device manufacturing. Silicone is widely used in urinary catheters and some small-diameter intravenous catheters—two key focus areas for HAI regulation. Integrating the active into the silicone material at an early stage in the process, rather than applying it afterwards, gives a medical device manufacturer better control of variables to achieve the desired release profile, such as an initial burst of active, a controlled rate of release over months or no release. Bulk loading also avoids performance issues, such as delamination from poor adhesion, which can occur with coatings, and helps to streamline production because it is performed prior to device manufacturing.
However, bulk loading of actives in silicone is a specialized technology that is best performed by a silicone supplier who has several decades of experience in manipulating complex chemistries to achieve a specific result. One reason is the inherent incompatibility between silicone, which is hydrophobic, and most popular antimicrobials, which are hydrophilic. The process of bulk loading, stabilization, and customized release can require sophisticated chemistry and specialized techniques to ensure uniform distribution and compatibility within the silicone matrix. Key considerations include particle size, particle density, and the use of excipients. On the other hand, this expertise in compatibility and tailored performance opens the door to bulk loading of new actives (beyond silver, for example) or unique combinations of actives that can provide the device maker with a competitive advantage.
Use Cases for Silicones with Bulk-Loaded Actives
Soft skin adhesive (SSA) technology, based on silicone gels first patented by Dow Corning in 1989, now finds wide application in advanced wound care dressings. Silicone SSA adheres well to skin but not to the wound bed (surface) or hair, avoiding damage and discomfort when changing the dressing. Silicone gel can be thought of as a lightly crosslinked (as compared to silicone elastomer) matrix that is swollen in a fluid comprised of long-chain silicone molecules. The crosslinked matrix helps to give the adhesive just the right amount of strength and cohesive body, while the fluid, called the “diluent,” provides softness. Silicone provides a better alternative than acrylics, which can cause skin sensitivities and are generally less gentle. Following are some examples of medical device applications where bulk loading of actives into a silicone material could help device makers deliver enhanced protection against HAIs.
SSA for wound dressing: A silicone gel adhesive that has been bulk loaded with antimicrobials, such as silver and/or chlorhexidine salts, could be applied to a polymer film substrate and used for wound care. (See Figure 1) Bulk loading of the active within the silicone gel matrix is necessary to preserve tack and other adhesion properties. Imagine the effect on these properties that a further coating or impregnation step would have. A coating would separate the adhesive from skin, preventing adhesion. Carriers for impregnation would extract silicone diluent from the gel, reducing the adhesive property known as tack.
Soft skin adhesive for draping surgical incision sites: To help avoid introduction of bacteria at the site of a surgical incision, a drape made with a silicone SSA that has been bulk loaded with antimicrobial actives could be placed over the target incision site. The surgeon makes the incision through the drape, (hence the name “incise drape”), ensuring protection of the area. This type of film dressing could also be used to secure a vascular catheter.
Urinary catheters: Due to population aging and health issues such as obesity, this market is expected to reach $250 million by 2016, according to a 2010 report from iData Research Inc. Currently, the small percentage of urinary catheters that feature antimicrobial protection use either coatings or impregnation. Using bulk-loaded silicone materials would eliminate a processing step, help to reduce manufacturing costs, and enable precise, controlled release over an extended period for ongoing protection. Similarly, antimicrobial wound drains could be easily manufactured. (See Figure 2)
Pacemaker components: Implanted medical devices, such as pacemakers, can develop biofilm infections. A silicone encapsulant that is bulk loaded with an antimicrobial agent could encase the pacemaker to help prevent formation of biofilm infections. Steroideluting silicone rings on pacemaker leads and silicone grommets help minimize inflammation of the cardiac muscles and decrease acute stimulation thresholds. (See Figure 3)
Diverse Actives Suitable for Bulk Loading
One of the advantages of the bulk loading process is its versatility. Many types of antimicrobials—and other actives—can be used with silicone elastomers. Although silver is a popular antimicrobial choice, it is expensive. Alternatively, manufacturers might choose biguanides, antibiotics, quaternary ammonium compounds, and other oligodynamic metals, such as zinc compounds. Because certain agents target specific pathogens, while others may exacerbate antibiotic-resistant strains, such as MRSA, the many possibilities for bulk loading of actives add to the value of this approach.
Beyond antimicrobials, creative use of other bulk-loaded actives can provide notable benefits to almost any device using silicone. For example, imagine contact lenses that already have antihistamine in them, negating the need for those pesky drops; or joint replacement implants for arthritic fingers and toes that include an anti-inflammatory agent. Antiinfective septa and needle-less access ports could be injection molded with liquid silicone rubber as they were before, but with a bulk-loaded active incorporated.
Bulk loading of actives in silicone adhesives and elastomers is a fresh strategy for combating device-related infections and other medical device issues to reduce concomitant mortality and morbidity. It can provide many benefits to manufacturers, ranging from the competitive advantage of adding actives to silicone components that previously lacked them, the capital and time savings associated with eliminating processing steps, and improving the performance and release profile of these actives vs. traditional coatings and impregnation. Device OEMs and contract manufacturers alike should contact silicone experts like Dow Corning Healthcare to discuss their application requirements.
This article was written by Jim Curtis, Senior Research & Product Development Specialist, Active-Loaded Materials Program, Healthcare Science & Technology, Dow Corning Corporation, Midland, MI. For more information, Click Here