| Popis: |
Considerable advances have been made in the field of drug delivery technology over the last three decades, resulting in many breakthroughs in clinical medicine. However, important classes of drugs have yet to benefit from these technological successes. One of the major requirements for an implantable drug delivery device is controlled release of therapeutic agents, especially biological molecules, at a constant rate over an extended period of time (i.e. a zero order release kinetics). Another significant challenge in drug delivery is to engineer a delivery system that can deliver drug in a manipulated non-zero order fashion such as pulsatile, ramp or delivery on demand. The goal of this research is to deliver technological innovations to address these requirements. Silicon was chosen as a carrier vehicle and nanochannel delivery systems (nDS) of progressively increasing degrees of functionality were conceived. The fundamental embodiment of the first device, nDS1, employs high-precision nanoengineered clefts to yield the long-term zero-order release of therapeutic agents. This device was designed and fabricated targeting four nanochannel sizes. These were 20 nm, 40 nm, 60 nm and 100 nm. The achieved nanochannel heights measured by Atomic Force Microscope (AFM) were 18 nm, 43 nm, 70 nm, and 108 nm, respectively. Glucose diffusion through a nominal 100 nm channel for a period of 15 days, through a nominal 60 nm channel for a period of 5 days and interferon-alpha (IFN-alpha) release through a nominal 100 nm channel for a period of 7 days showed a zero order release profile through this device. Further, it was proved that IFN-alpha preserves its functional activity after being released through this device. Next, the top substrate of the nDS1 device was replaced with a glass substrate (nDS1g) for improved bonding and a visual observation of fluid flow through the nanochannels of the device. Another implantable drug delivery system (nDS2) that is capable of being integrated with an external electronic circuit of interest was designed and a fabrication process flow was developed. This device has integrated electrodes and the concept of drug delivery is based upon electrokinetic flow of molecules through the nanochannels of the device. |
