Micro- and nano-fabricated implantable drug-delivery systems

Abstract

Implantable drug-delivery systems provide new means for achieving therapeutic drug concentrations over entire treatment durations in order to optimize drug action. This article focuses on new drug administration modalities achieved using implantable drug-delivery systems that are enabled by micro- and nano-fabrication technologies, and microfluidics. Recent advances in drug administration technologies are discussed and remaining challenges are highlighted.

Figure 1. Reservoir-based drug-delivery approaches

(A) Four embodiments of passive-diffusion-based reservoir drug-delivery devices. The release rate and/or onset of delivery of drug stored or produced in the reservoir is regulated by a membrane that may be modified to be nanoporous, biodegradable, electrochemically or electrically removable (metal thin film), or shrunken by application of thermal energy (hydrogel block valve). (B) Four embodiments of actively driven reservoir drug-delivery devices. The mechanism by which drug is actively displaced from the reservoir is depicted including electrolytically generated bubbles, thermally generated bubbles, preloaded pressure difference, or magnetic modulation of membrane displacement and delivery orifice dimensions.

Figure 2. Passive micropumping approaches

(A) The operation of an osmotically powered pump. A semipermeable membrane regulates water uptake by the osmotic driving agent, which results in a pressure increase that deflects a flexible diaphragm. The diaphragm in turn displaces the drug stored in the adjacent reservoir. (B) A spring-powered pump concept. External mechanical compression of a compliant drug reservoir provides the pressure differential required to displace drug from the reservoir. Drug delivery is regulated by a valve in line with the pump outlet.

Figure 3. Active pumping approaches

(A) The fundamental configuration of a reciprocating diaphragm pump showing the major components. Pumping is achieved when the reciprocating actuator (pumping mechanism) alternates between the supply and discharge states. During these stages, the drug chamber above the diaphragm is filled and emptied, respectively, as regulated by two opposing one-way valves. (B) Peristaltic pump consisting of three pumping chambers. Each chamber is separately controlled and activated in a prescribed sequence, such as the one illustrated, to squeeze drug in one direction.