TY - JOUR
T1 - Leveraging nanochannels for universal, zero-order drug delivery in vivo
AU - Ferrati, Silvia
AU - Fine, Daniel
AU - You, Junping
AU - De Rosa, Enrica
AU - Hudson, Lee
AU - Zabre, Erika
AU - Hosali, Sharath
AU - Zhang, Li
AU - Hickman, Catherine
AU - Sunder Bansal, Shyam
AU - Cordero-Reyes, Andrea M.
AU - Geninatti, Thomas
AU - Sih, Juliana
AU - Goodall, Randy
AU - Palapattu, Ganesh
AU - Kloc, Malgorzata
AU - Ghobrial, Rafik M.
AU - Ferrari, Mauro
AU - Grattoni, Alessandro
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Drug delivery
KW - Implantable device
KW - Nanochannel
KW - Transplantation
UR - http://www.scopus.com/inward/record.url?scp=84887164660&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84887164660&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2013.09.028
DO - 10.1016/j.jconrel.2013.09.028
M3 - Article
C2 - 24095805
AN - SCOPUS:84887164660
VL - 172
SP - 1011
EP - 1019
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 3
ER -