The medical device industry has undergone significant evolution over the past several years -- and drug delivery is moving to the forefront. With the rapid adoption of drug-eluting stents, the medical industry has recognized the value coupling drug delivery with a medical device can bring to patient care. Devices that enable the controlled release of pharmaceutical and biological agents within the body directly to the sites where they are needed could revolutionize many applications, such as spinal cord repair, nerve generation, and tumor remediation.
This article will explore the latest advancements in extrusion technology, which are enabling the next generation of drug delivery. It will also explore some of the medical applications that stand to be impacted most by this technological advancement.
Biodegradable fibers: New format for drug delivery
Novel processes which allow for fiber extrusion at room temperature enable an entirely new format for drug delivery -- via biodegradable fibers. Traditionally, fiber extrusion occurred at high temperatures, limiting the types of drugs and biological agents that could remain viable. Now, with extrusion at room temperature, the biological activity of a wide variety of drugs and therapeutics can be preserved.
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.
The use of fibers offers several unique advantages over traditional drug-delivery formats. The long cylindrical geometry of fibers provides a slower release rate than a spherical geometry of the same radius, resulting in an inherently longer therapeutic window for similar drug concentrations. Also, because fibers are readily implantable and maintain positional stability, they offer an unparalleled advantage when targeting specific tissue sites, such as solid tumors.
Additionally, fibers decrease the risk to patients because the fiber is removable (in the rare case of an adverse reaction), whereas microspheres and nanoparticles are not. Third, fiber extrusion is a very controlled process, yielding more uniform size distribution than typically found in other formats. Finally, multi-layered, co-axial fibers may be readily produced with each layer containing a unique drug and polymer combination, thus enabling tailored release kinetics for multiple drugs in a single fiber.
Creating drug-loaded fibers using wet spinning techniques
Wet spinning processes involve injecting a polymer solution under pressure through a spinneret into a coagulating bath. This bath consists of a solution that is highly miscible with the solvent used to dissolve the polymer yet is a nonsolvent for the polymer. As the polymer solution stream enters the coagulating bath, the solvent diffuses from the solution stream into the bath, locally increasing the polymer concentration. At the same time, the polymer stream is exposed to the nonsolvent of the coagulation bath. This combined effect causes the polymer molecules to precipitate out of the 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, but heating as low as body temperature can easily be used in wet spinning. In this case, the residual solvents (and nonsolvents from the coagulating bath) provide the molecular mobility required to allow the polymer chains to align and create entanglement sites that provide high mechanical properties to the fiber.
Though the solvents may aid the processing of the fibers to allow the process to occur anywhere from room to body temperature, exposure to the solvents and nonsolvents used during extrusion could destroy incorporated drugs or biological agents. But it is possible to protect the drug from the solvent. Enveloping it in an emulsion or a nanoparticle, or trapping it within a hydrogel, for example, adequately safeguards the drug from the solvent environment. Prior to use in medical applications, however, the solvents must be cleaned from the fibers.