Nanoengineered implantable devices for controlled drug delivery

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. The creation of drug delivery devices that are capable of delivering therapeutic agents that cannot be delivered by any other means or that have diminishment of therapeutic efficacy when given by other means of administration is a challenge in this area of research, while at the same time the financial interest because of the continuously growing drug delivery market cannot be ignored. One of the major requirements for an implantable drug delivery device is controlled release of therapeutic agents, especially biological molecules, as a continuous delivery over an extended period of time. The goal here is to achieve a continuous drug release profile consistent with zero-order kinetics where the concentration of drug in blood remains constant throughout the delivery period. 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 or ramp or some other pattern.; 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 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. This device can be connected to a pre-programmable circuit to achieve manipulable delivery, can be connected to a wireless circuit to achieve external control of delivery on demand, or can be connected with an implantable sensor through a feedback control circuit to achieve a contained system where the delivery can be triggered upon the requirement of the physiological system. These devices have potential to improve therapeutic efficacy, diminish potentially life-threatening side effects, improve patient compliance, minimize the intervention of healthcare personnel and reduce the duration of hospital stays.