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Enabling the Next Generation of Implantable Devices Through Fiber Extrusion Processes

Tue, 07/02/2013 - 11:29am
Dr. Kevin Nelson, Founder and CSO, TissueGen

Enabling the delivery of a drug directly to the treatment area significantly enhances effectiveness. A well-known example of this localized approach is the drug-eluting stent. Today, innovative new devices incorporating drug-loaded fibers into implantable textile structures have the potential to deliver this type of benefit to an array of therapeutic treatments.

Wet-extruded fiber loaded with a virus for the production of green fluorescent protein implanted into a human pancreatic tumor that was grown in an immune compromised animal.Incorporating drug-loaded fibers in implantable textile structures for medical device applications has the potential to add significant value. These fibers 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. However, the types of drugs and therapeutic agents that could be loaded to fibers while remaining viable have traditionally been limited by the extrusion process itself. Today, however, innovative extrusion methods are enabling drug loading of wet-extruded fibers for use in implantable devices for localized drug delivery within the body. These extrusion methods are a type of solution spinning.

Solution Spinning vs. Melt-Extrusion Methods
Solution spinning is a process of extruding fibers from polymer solutions whereby the solution is created through dissolving the polymer in a solvent at room temperature. In contrast, traditional melt-extruded polymer fibers are limited by the high processing temperatures required in the extrusion process (often in excess of 200°C for many medical grade polymers). Melt extrusion processing temperatures exceed the tolerance of the vast majority of pharmaceutical and biological therapeutic agents. Fortunately, solution spinning overcomes the challenges of high temperature associated with melt-extrusion. There are numerous types of solution spinning; however, a particularly promising method is wet spinning.

Wet Spinning to Create Drug-Loaded Fibers
Wet spinning is the process of injecting polymer solution under pressure through a spinneret into a coagulating bath. The coagulating bath consists of a solution that is highly miscible with the solvent used to dissolve the polymer, yet is a non-solvent for the polymer. As the polymer solution stream enters the coagulating bath, the solvent diffuses from the solution stream into the coagulating bath, locally increasing the polymer concentration. Simultaneously, the polymer stream is exposed to the non-solvent of the coagulation bath. This combined effect causes the polymer molecules to precipitate out of solution, forming a solid fiber. The polymer fiber is then pulled from the coagulation bath and taken through a number of draw stations where the fiber is stretched. These draw stations typically include ovens to heat the fiber during the pulling (drawing) process. However, wet spinning uses heating as low as body temperature. In wet spinning, the residual solvents (and non-solvents from the coagulating bath) provide the molecular mobility required to allow the polymer chains to align and create entanglement sites, resulting in high mechanical properties. While the solvents aid the processing of the fibers to allow the process to occur anywhere from room to body temperature, exposure to the solvents and non-solvents during extrusion may destroy incorporated drugs or biological agents. However, it is possible to protect the drug from the solvent by enveloping the drug in an emulsion or a nanoparticle, or trapping it within a hydrogel or other types of excipients. Prior to incorporation in medical applications, however, the solvents must be completely cleaned from the fibers. Several processes can be used to effectively remove residual solvent to levels of as low as 1/10 of the allowable limit set by FDA guidelines without exposing the loaded drugs or biologics to temperatures higher than body temperature, and thus preserving their viability.

PLGA co-extruded over a 0.005 in. nitinol wire for large drug reservoir and long-term delivery.An additional and significant advantage of wet spinning processing is the broad range of polymers that may be processed, including both synthetic and biopolymers. For example, core-sheath format fibers can be made with a carbohydrate-based hydrogel interior and a hydrophobic synthetic (i.e., PLLA or PLGA) sheath. An advantage of fibers produced through wet spinning processing that are inherently phase-separated (whether core-sheath or other formats) is the resulting control over release kinetics of the drug of interest, as well as increased protection of hydrophilic drugs and biological agents.

Advantages of Wet Spinning Fibers for Implantable Drug Delivery
Engineering techniques such as altering the porosity of the fiber can dramatically change the release kinetics of the fiber. For example, by appropriate choices of solvent and non-solvent systems, the fibers can have inherent porous or solid internal morphology. The method of protecting the drug also changes the release kinetics. The shape of the release kinetics profile can also be tailored by extruding blends of polymers with different degradation rates. All of these control parameters result in an unparalleled ability to control drug delivery.

The controlled, localized drug delivery capability offered by wet-spinning fibers enables medical device designers to locally affect the body’s response to the device. Depending on the choice of drug, it is possible to mitigate unwanted responses and promote desired responses. Since all drug interaction occurs at the surface of the device, rather than through systemic distribution, drugs may be administered locally with very little exposure to the rest of the body, as typically only cells within a few millimeters of the device are impacted by the drug.

Beyond use in medical devices, drug-loaded fibers provide excellent drug delivery depots where precise placement within the body is desired, such as within a solid tumor. In these cases, drug-loaded fibers may deliver a range of drugs from small pharmaceuticals to viruses for periods up to six months.

These drug-loaded, wet-spun fibers also provide excellent scaffolding for tissue engineering and regenerative medicine applications. No other method enables the ability to deliver drugs to the cells on and around a single specific fiber. This ability to control three-dimensional drug distribution to spatial tolerances of less than 1.0 mm provides a significant tool to accelerate the development of tissue engineering and regenerative medicine applications.

Conclusion
The medical device industry has experienced significant evolution in recent years and drug delivery technology promises to accelerate development. Similar to the revolutionary impact drug eluting stents had in the field of cardiovascular medicine, a wide range of medical applications stand to significantly benefit from the incorporation of wet-spun drug-loaded fibers.

For more information, visit www.tissuegen.com.

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