Leveraging nanochannels for universal, zero-order drug delivery in vivo.
J Control Release
; 172(3): 1011-9, 2013 Dec 28.
Article
in En
| MEDLINE
| ID: mdl-24095805
ABSTRACT
Drug delivery is essential to achieve effective therapy. Herein we report on the only implantable nanochannel membrane with geometrically defined channels as small as 2.5 nm that achieves constant drug delivery in vivo. Nanochannels passively control the release of molecules by physico-electrostatic confinement, thereby leading to constant drug diffusion. We utilize a novel design algorithm to select the optimal nanochannel size for each therapeutic agent. Using nanochannels as small as 3.6 and 20 nm, we achieve sustained and constant plasma levels of leuprolide, interferon α-2b, letrozole, Y-27632, octreotide, and human growth hormone, all delivered at clinically-relevant doses. The device was demonstrated in dogs, rats, and mice and was capable of sustaining target doses for up to 70 days. To provide evidence of therapeutic efficacy, we successfully combined nanochannel delivery with a RhoA pathway inhibitor to prevent chronic rejection of cardiac allografts in a rat model. Our results provide evidence that the nanochannel platform has the potential to dramatically improve long-term therapies for chronic conditions.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pharmaceutical Preparations
/
Drug Delivery Systems
/
Nanostructures
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
J Control Release
Journal subject:
FARMACOLOGIA
Year:
2013
Document type:
Article
Affiliation country:
United States