Silk Reservoir Implants for Sustained Drug Delivery
Alexander J. Wolfe, Jeffrey Guasto, Fiorenzo G. Omenetto, David L. Kaplan
Abstract
Biomaterial implants for the sustained delivery of therapeutics can be utilized to deliver drugs at near-constant rates over extended time frames to provide an alternative to daily oral medications. The biomaterials used to construct these systems, however, are often not bioresorbable and thus require a secondary surgery for removal from the body, and fabrication of these systems may require the use of harsh chemical solvents. To address these shortcomings, a fabrication process was developed to generate biodegradable drug reservoir systems from regenerated silk fibroin protein solution (23% w/v). The tubular systems, with an inner diameter of 2.0 mm and wall thickness < 250µm, were developed using an all-aqueous solution-gel-solid phase transition curing process. Two different clinically-relevant therapeutics were released at near-constant rates for 30 days (> 100µg/day). The protein secondary structure of the devices consisted of 40% crystalline beta sheet. Mechanically, radial compression (1mm/min) of unloaded systems demonstrated Young's moduli similar to cancellous (spongy) bone (100 to 250 MPa) and the systems showed good recovery under cyclic compression (to 17.5% strain). The devices could be generated in complex shapes (e.g., hollow cylinders) via an additive molding process, offering the potential for drug delivery but also for broader applications in tissue engineering and diagnostics.