PROGRAMMABLE DRUG DELIVERY DEVICES

Clinical Impact of Medical Device Related Infections: Implantable medical devices inherently increase the risk of infection either through the implant procedure itself or as an access point to external microorganisms. Chronic infections place a major burden on the healthcare system with some estimates as high as $12 billion per year for the US alone. This is caused by patients spending more time in the hospital, requiring more doctor and nurse time and the use of expensive systemic antibiotics as more aggressive treatment options are explored.

In recognition of this high cost, the Center for Medicare and Medicaid Services (CMS) implemented restrictions in October of 2008 for hospital-acquired infections. In particular, surgical-site infections involving catheters used in treatment of urinary tract infections or bloodstream infections are not reimbursed. This decision has led to increased vigilance at hospitals to control infections and has also increased the awareness of and interest in anti-microbial solutions for implantable devices.

Infection caused by implantable medical devices is often a result of biofilm development on the device surfaces. Microorganisms adhere to the surface of the device anchoring themselves and facilitating the attachment of other microbes which leads to further colonization and formation of polymicrobial environment with increased pathogenic effect. Once the biofilm is developed, it is increasingly difficult to eliminate and the cells become more antibiotic resistant. Biofilm infections have been estimated to be 1,000 times more resistant to antibiotics than conventional infections.

The current state of the art in infection control devices include some form of silver containing coating. The challenge is that while effective in the short term, silver coatings have limited duration and may not last long enough to prevent infections in devices that are implanted for more than 7 days. Silver is also non-selective.

Epidel^TM Solution: Epidel anti-infective polymers are long chain polymers for implantable medical devices that release pharmaceuticals to fight infection. By combining various pairings of anti-microbial agents, Epidel has demonstrated ability to control a broad range of microbes over an extended period of time. Further, since the pharmaceuticals are built into the backbone of the polymer itself, Epidel is compatible with a number of manufacturing processes including fiber spinning, durable dip coating, electro spinning and molding which provides broad applicability across a wide range of implantable devices.

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Epidel in fiber form is appropriate for a number of different applications including catheter cuffs, fixation devices, hernia mesh, incontinence slings, sutures, bandages, etc. The polymer is first spun into fiber and then punched and needled with a base material to create a non-woven fabric which can then be cut and fashioned into the applicable device. The following depicts the creation of an Epidel catheter cuff.

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Various in vitro and in vivo studies have been performed on the Epidel fiber material in a catheter cuff against a Dacron control. The first series of experiments started with a challenge of 103 Colony Forming Units (CFUs) per mL for various microbes. Microbial growth (CFUs/mL) was tracked over 144 hours. Over this period and with the various microbes, the Epidel cuff significantly outperformed the Dacron cuff as illustrated by the series of SEMs below.

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In a percutaneous rabbit study, a small subcutaneous pocket was made and a Dacron control cuff or Epidel cuff was placed in the pocket. In one group, an inoculation of 106 MRSA was placed on top of the surgical site and animals were housed for 1 week after which the catheter was excised and sectioned, and plate counts were conducted. In the second group, after 1 week an inoculation of 106 MRSA was placed on top of the surgical site and animals were housed for 1 additional week after which the catheter was excised and sectioned, and plate counts were conducted. The Epidel cuff demonstrated a 98% reduction of bacterial colonization relative to the Dacron control.

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Epidel can also be used as a coating for implantable devices such as urinary and venous catheters and can be coated on a variety of medical grade polymers including silicone, polyurethanes, and PVC. The coating is uniform, sterilizable and can be present on both the extra-lumenal and intra-lumenal surfaces.

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In the SEM example below, Epidel coated PVC tubing is shown relative to control PVC tubing after 192hr incubation with x103 P. aeruginosa. The PVC tubing is rife with bio-film both inside and outside of the tube while the Epidel coated tubing is clean.

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Epidel^TM Applications: Minimally invasive applications include catheter fixation devices, bandages and sutures. Moderately invasive applications include urinary catheters, vascular access catheters, hernia mesh and incontinence sling.

Kinesyx^TM Solution: Kinesyx is an extension of the Endexo platform. It is a versatile technology platform with a broad range of formulations, which can provide compatibility with different class of pharmaceuticals and biologics. A sustained or transient release profile can be achieved depending on the formulation selection. Kinesyx™ Bioactive Oligomers provide an ideal platform for drug delivery due to the benefits of the fluorine chemistry, the flexible molecular structure, the ability to tailor both pharmaceutical release and polymer residency and the unique physical, chemical and biological properties. Kinesyx™ molecules are polyurethane oligomers with fluorinated segments, and can be designed to work with a number of different pharmaceuticals with specific release requirements.

Fluorine provides a number of benefits for the Kinesyx™ oligomers as a drug delivery platform. Exceptional chemical and biological inertness with reduced plasma protein activation increases the overall safety profile and offers a unique clinical impact factor for this delivery platform.

Kinesyx^TM Results: In vitro studies demonstrate the ability to tailor the pharmaceutical release profile based on the Kinesyx™ formulation chosen to target transient or sustained release profile. Long term, sustained drug release can be achieved with one class of Kinesyx™ formulation while a more immediate release can be achieved with others. The graph demonstrates the percentage release of Paclitaxel (PTx) over 24 hours with various Kinesyx™ formulations.

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One of the unique aspects of the Kinesyx^TM oligomer is its bio-elimination properties. Because of the relatively small size of the molecule, it can be eliminated through the renal system and does not have to degrade like other larger polymers before it can be absorbed or released.

Bio-compatibility studies have been conducted on a number of Kinesyx^TM formulations to demonstrate blood compatibility, inflammatory response and vascular compatibility. Further studies have been conducted to assess pharmaceutical loading and release, coating capability and long term residency. These are available to partners interested in assessing the Kinesyx^TM technology. Interface Biologics is currently investigating Kinesyx^TM applications in the cardiology, oncology and ophthalmology fields.

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Kinesyx^TM Applications Include: Drug eluting stents, drug eluting balloons (peripheral vs. coronary focus), ophthalmology and targeted oncology