Microfabricated nanochannel implantable drug delivery devices: trends, limitations and possibilities

This is a review of the application of microfabrication technologies, borrowed from the semiconductor industry, to drug delivery implants incorporating structures in the nanometer dimension. In the futuristic ideal, these systems would involve the implantation of precisely microfabricated drug delivery systems with nanopores, nanochannels and/or nanoreservoirs fabricated from silicon, coupled with electronic sensing and actuator systems, for the precise, timed and/or targeted delivery of drugs. After more than a decade in conceptualisation and experimentation, four systems that have commercial potential are discussed: i) implantable microchips with on-demand microdosage for one or more therapeutic agents under internal control or external control using a wireless link; ii) nanopore pumps, implantable titanium pumps, consisting of a drug reservoir with a nanopore-release membrane, capable of delivering potent small or macromolecules at constant serum levels for sustained periods of time; iii) nanocages, microfabricated nanopore immunoisolation chambers for cellular implants, capable of natural feedback-controlled delivery of proteins and peptides; and iv) nanobuckets, micromachined silicon porous particles with drug-loading capacity and targeting ligands for localised delivery. Each of the systems, along with future trends in microfabrication manufacturing, limitations and possibilities, are discussed.