Nanochannel Technology for Constant Delivery of Chemotherapeutics: Beyond Metronomic Administration

The purpose of this study is to demonstrate the long-term, controlled, zero-order release of low- and high-molecular weight chemotherapeutics through nanochannel membranes by exploiting the molecule-to-surface interactions presented by nanoconfinement. Silicon membranes were produced with nanochannels of 5, 13 and 20 nm using standardized industrial microfabrication techniques. The study of the diffusion kinetics of interferon alpha-2b and leuprolide was performed by employing UV diffusion chambers. The released amount in the sink reservoir was monitored by UV absorbance. Continuous zero-order release was demonstrated for interferon alpha-2b and leuprolide at release rates of 20 and 100 mu g/day, respectively. The release rates exhibited by these membranes were verified to be in ranges suitable for human therapeutic applications. Our membranes potentially represent a viable nanotechnological approach for the controlled administration of chemotherapeutics intended to improve the therapeutic efficacy of treatment and reduce many of the side effects associated with conventional drug administration.