Nanochannel technology for constant delivery of chemotherapeutics: beyond metronomic administration.
OBJECTIVE
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.


METHODS
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 α-2b and leuprolide was performed by employing UV diffusion chambers. The released amount in the sink reservoir was monitored by UV absorbance.


RESULTS
Continuous zero-order release was demonstrated for interferon α-2b and leuprolide at release rates of 20 and 100 μg/day, respectively. The release rates exhibited by these membranes were verified to be in ranges suitable for human therapeutic applications.


CONCLUSIONS
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.
Grattoni
Alessandro
A
Department of NanoMedicine and Biomedical Engineering (nBME), The University of Texas Medical School at Houston, Houston, Texas, USA.
Shen
Haifa
H
Fine
Daniel
D
Ziemys
Arturas
A
Gill
Jaskaran S
JS
Hudson
Lee
L
Hosali
Sharath
S
Goodall
Randy
R
Liu
Xuewu
X
Ferrari
Mauro
M
D000970:Antineoplastic Agents / Q000008:administration & dosage; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004058:Diffusion; D016503:Drug Delivery Systems / Q000295:instrumentation*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D016729:Leuprolide / Q000008:administration & dosage; D008567:Membranes, Artificial; D049329:Nanostructures / Q000737:chemistry*; D036103:Nanotechnology / Q000295:instrumentation* / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy; D010316:Particle Size; D011994:Recombinant Proteins
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008567:Membranes, Artificial; D011994:Recombinant Proteins; D016729:Leuprolide