Intelligent drug-delivery devices based on micro- and nano-technologies.

This review focuses on the current drug-delivery modalities in R&D, as well as commercially available. Intelligent drug-delivery systems are described as novel technological innovations and clinical approaches to improve conventional treatments. These systems differ in methodology of therapeutic administration, intricacy, materials and patient compliance to address numerous clinical conditions that require various pharmacological therapies. These systems have been primarily described as active and passive microelectrical mechanical system devices, injectors and nanoparticle-based therapies, optimized to tailor specific pharmacokinetic profiles. The most critical considerations for the design of these intelligent delivery systems include the controlled release, target specificity, on-demand dosage adjustment, mass transfer and stability of the pharmacological agents. Drug-delivery systems continue to be developed and enhanced to provide better and more sophisticated treatments, promising an improvement in quality of life and extension of life expectancy.

Electro-thermally induced structural failure actuator (ETISFA) for implantable controlled drug delivery devices based on micro-electro-mechanical-systems.

A new electro-thermally induced structural failure actuator (ETISFA) is introduced as an activation mechanism for on demand controlled drug delivery from a Micro-Electro-Mechanical-System (MEMS). The device architecture is based on a reservoir that is sealed by a silicon nitride membrane. The release mechanism consists of an electrical fuse constructed on the membrane. Activation causes thermal shock of the suspended membrane allowing the drugs inside of the reservoir to diffuse out into the region of interest. The effects of fuse width and thickness were explored by observing the extent to which the membrane was ruptured and the required energy input. Device design and optimization simulations of the opening mechanism are presented, as well as experimental data showing optimal energy consumption per fuse geometry. In vitro release experiments demonstrated repeatable release curves of mannitol-C(14) that precisely follow ideal first order release kinetics. Thermally induced structural failure was demonstrated as a feasible activation mechanism that holds great promise for controlled release in biomedical microdevices.

Medical applications of implantable drug delivery microdevices based on MEMS (Micro-Electro-Mechanical-Systems).

Drug delivery microdevices based on MEMS (Micro-Electro-Mechanical-Systems) represent the next generation of active implantable drug delivery systems. MEMS technology has enabled the scaling down of current delivery modalities to the micrometer and millimeter size. The complementary use of biocompatible materials makes this technology potentially viable for a wide variety of clinical applications. Conditions such as brain tumors, chronic pain syndromes, and infectious abscess represent specialized clinical diseases that will likely benefit most from such drug delivery microdevices. Designing MEMS microdevices poses considerable technical and clinical challenges as devices need to be constructed from biocompatible materials that are harmless to human tissue. Devices must also be miniaturized and capable of delivering adequate pharmacologic payload. Balancing these competing needs will likely lead to the successful application of MEMS drug delivery devices to various medical conditions. This work reviews the various factors that must be considered in optimizing MEMS microdevices for their appropriate and successful application to medical disease.

An implantable MEMS drug delivery device for rapid delivery in ambulatory emergency care.

We introduce the first implantable drug delivery system based on MEMS (Micro-Electro-Mechanical-Systems) technology specifically designed as a platform for treatment in ambulatory emergency care. The device is named IRD(3) (implantable rapid drug delivery device) and allows rapid delivery of drugs. Vasopressin was used as a model drug for in vitro tests as it is a commonly used drug for cardiac resuscitation. Experimental results reveal that the IRD(3) provides an effective method for rapid delivery without significant drug degradation. Several medical uses and delivery modalities for IRD(3) are proposed.