(575a) Solvent-Free Drug Encapsulation for Zero-Order Immunosuppressive Delivery from Three-Dimensional Devices

Mitigation of immune responses is one of the major challenges in implanting medical devices. Traditionally, anti-inflammation drugs are taken by injection or oral administration to suppress the immune responses. However, injections increase the risk of infection and patients’ discomfort; and oral administration has low efficiency in drug delivery and often causes side effects. There is an unmet need to incorporate immunosuppressive drugs onto three-dimensional devices for effective delivery at the periphery of the devices. We encapsulated dexamethasone, a potent steroidal immunosuppressive drug, using a one-step, solvent-free method that formed coatings directly from the vapor phase onto device surfaces. By eliminating solvent use in the encapsulation process, the release profile of dexamethasone changed from two-day burst release to 60-day linear release at the same coating parameters. The significant change in drug release kinetics was attributed to the efficient construction of mass transfer barrier around the drug using the vapor-based encapsulation, while the solution-based processing re-distributed and mixed the drug into the barrier coating, leading to burst release. The drug release kinetics can be regulated by crosslinking the encapsulation coating in situ, which not only provided dexamethasone release towards therapeutic dose below 2.0 µg/day but also enabled more than 90% reduction in daily release variation. We further demonstrated that the wettability of encapsulation coatings played an important role in determining the drug release kinetics. At a moderate crosslinking degree, as the contact angle of encapsulation coatings increased from 75.4° to 86.0°, the release rate of dexamethasone reduced from 24.4 µg/day to 2.7 µg/day. In addition, we studied the DEX release kinetics using the Korsmeyer-Peppas model. The drug release rate was linearly correlated with the drug load and the thickness of the encapsulation coating, providing additional regulation of drug release kinetics The immunosuppressive effect of the released dexamethasone was assessed using microglia cell studies. On day one, the microglia activation expression was suppressed by 86% and 96% on encapsulated dexamethasone at 50 and 100 µg/cm², respectively. On day three, there was no significant difference between non-stimulated microglia and stimulated microglia on encapsulated dexamethasone at 50 and 100 µg/cm². In conclusion, We demonstrated a solvent-free encapsulation for the immunosuppressive drug that successfully eliminated the burst release during the drug delivery from 3D devices, and the drug release rate can be regulated by the coating wettability, encapsulation crosslinking, drug load, and coating thickness. This novel solvent-free method can be extended to the encapsulation of other pharmaceutical drugs, providing a new platform to achieve sustained, zero-order drug release from three-dimensional medical devices.