Expanding the possibilities of implantable drug delivery.
Drug delivery has become a major — and still rapidly growing — segment of the medical device industry, with medical devices that enable controlled, internal release of pharmaceuticals to targeted surgical sites presenting enormous opportunities. The widespread adoption of drug-eluting stents is evidence that the medical industry sees the benefit of coupling drug delivery capabilities with medical devices, which may improve patient outcomes.
Incorporating drug-loaded fibers in implantable textile structures for medical device applications has the potential to revolutionize how pharmaceuticals and even biologic agents can be delivered. These fibers may allow for improved device performance resulting in faster healing, improved patient compliance, and lower negative outcomes at relatively low cost by adding drug-delivery capabilities to new and existing devices across a variety of applications.
However, the types of drugs able to be successfully loaded to fibers while remaining viable have traditionally been limited by the mechanics of the extrusion process. In traditional melt-extrusion, the high temperatures required exceed the temperature tolerance of the vast majority of pharmaceutical and biological therapeutic agents. Now, the emergence of alternative wet extrusion methods is enabling drug loading of fibers at room temperature for use in implantable devices for localized drug delivery within the body.
Wet Spinning Fundamentals
Wet fiber extrusion is a very controlled process, yielding more uniform size distribution than the distribution typically found in other formats. Multi-layered, co-axial fibers may be readily produced with each layer containing a unique pharmaceutical and polymer combination, thus enabling tailored release kinetics for multiple pharmaceuticals in a single fiber.
Extrusion methods based on the fundamentals of wet spinning, coupled with drug protection technology, allow a variety of pharmaceuticals to be loaded into biodegradable fibers. Successful cases have included (but are not limited to):
- Aldose Reductase Inhibitor
- Copper Nanoparticles
Excellent Pharmaceutical Delivery Depots
Wet-extruded fibers are ideal for use in current and next-generation implantable medical devices. The localized pharmaceutical delivery capability of these fibers enables medical device designers to orchestrate the body’s response to the device. Depending on the choice of drug, it is even possible to mitigate unwanted reactions and promote desired responses.
Beyond use in medical devices, pharmaceutical-loaded fibers provide excellent pharmaceutical delivery depots where precise placement within the body is desired, such as within a solid tumor. Because fiber is both readily implantable and maintains positional stability, it offers an unparalleled advantage when targeting specific tissue sites.
Fibers can be extruded in monofilament, hollow, bi-component (core-sheath), and even gel-center filled formats, and also as flat, rectangular or ribbon shapes. Unlike traditional pharmaceutical delivery formats such as microspheres and nanoparticles, these fibers can provide both mechanical and pharmacological support from the same device – an incredible advantage over other modes of pharmaceutical delivery.
Significant Step Forward
When used as drug delivery depots, drug-loaded fibers may deliver therapeutic agents ranging from small pharmaceuticals to viruses. In vitro testing has shown delivery of a growth factor (protein-based therapeutic) for over 300 days. These drug-loaded, wet-extruded fibers also provide excellent scaffolding for tissue engineering and regenerative medicine applications. It is otherwise impossible to provide pharmaceutical delivery localized to the cells on and around a single specific fiber. This micro-control of pharmaceutical release provides a significant step forward in research in implantable pharmaceutical delivery.
The use of biodegradable fibers offers several other unique advantages over traditional pharmaceutical delivery formats. A long cylindrical geometry can provide a slower pharmaceutical release rate than a spherical geometry of the same radius, resulting in an inherently longer therapeutic window for similar pharmaceutical concentrations. Additionally, unlike microspheres and nanoparticles, fiber is removable in the rare case of an adverse patient reaction.
Pharmaceuticals may be administered locally with very little exposure to the rest of the body, as typically cells within a few millimeters of the device will be predominately impacted by the pharmaceutical. Thus, depending on the choice of pharmaceutical, the controlled, localized pharmaceutical delivery capability makes it possible to mitigate unwanted responses and promote desired responses.
Expanding the types of drugs that can be delivered internally can have significant beneficial implications for a variety of medical applications. For example, delivering biologics such as protein-based therapeutics can significantly broaden the indications treatable with drug-eluting fibers. As an example, the neurotrophin family of growth factor proteins may now significantly enhance peripheral nerve regeneration when delivered from a fiber. Similarly, delivering vascular endothelial growth factor may induce vascularization in the near vicinity of the fiber.
Delivering elastin promoting growth factors at the site of implantation can be ideal for facilitating dermal wound healing with the potential for reduced scar. Implantable fiber is also uniquely well suited for ocular drug delivery to help treat diabetic retinopathy, a complication of diabetes, which causes damage to the blood vessels of the tissue at the back of the retina.
Breakthroughs in fiber extrusion are now making it possible to load the widest variety of viable pharmaceuticals and biologics ever for implantable drug delivery. Allowing these agents to be delivered internally directly at targeted surgical sites has the potential to revolutionize the way many medical applications can be approached — presenting new opportunities for medical device manufacturers; providing doctors and surgeons with greater options for treatment approaches; and ultimately may improve patient outcomes in many cases.