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Fabrication of Sealed Nanostraw Microdevices for Oral Drug Delivery

Fox, Cade B. and Cao, Yuhong and Nemeth, Cameron L. and Chirra, Hariharasudhan D. and Chevalier, Rachel W. and Xu, Alexander M. and Melosh, Nicholas A. and Desai, Tejal A. (2016) Fabrication of Sealed Nanostraw Microdevices for Oral Drug Delivery. ACS Nano, 10 (6). pp. 5873-5881. ISSN 1936-0851. doi:10.1021/acsnano.6b00809.

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The oral route is preferred for systemic drug administration and provides direct access to diseased tissue of the gastrointestinal (GI) tract. However, many drugs have poor absorption upon oral administration due to damaging enzymatic and pH conditions, mucus and cellular permeation barriers, and limited time for drug dissolution. To overcome these limitations and enhance oral drug absorption, micron-scale devices with planar, asymmetric geometries, termed microdevices, have been designed to adhere to the lining of the GI tract and release drug at high concentrations directly toward GI epithelium. Here we seal microdevices with nanostraw membranes—porous nanostructured biomolecule delivery substrates—to enhance the properties of these devices. We demonstrate that the nanostraws facilitate facile drug loading and tunable drug release, limit the influx of external molecules into the sealed drug reservoir, and increase the adhesion of devices to epithelial tissue. These findings highlight the potential of nanostraw microdevices to enhance the oral absorption of a wide range of therapeutics by binding to the lining of the GI tract, providing prolonged and proximal drug release, and reducing the exposure of their payload to drug-degrading biomolecules.

Item Type:Article
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Xu, Alexander M.0000-0003-4877-4358
Additional Information:© 2016 American Chemical Society. Received: February 1, 2016; Accepted: June 7, 2016; Published: June 7, 2016. C.B.F. was supported by NIH Training Grant 5T32GM007175-37 and an ARCS Fellowship. Y.C. was supported by Grant 70NANB15H192 from the U.S. Department of Commerce, National Institute of Standards and Technology. C.L.N. was supported by NSF Graduate Research Fellowship DGE-1106400. R.W.C. was supported by NIH Training Grant 5T32DK007762-38. A.M.X. was supported by NSF Graduate Fellowship DGE-114747 and an NDSEG Fellowship. This work was partially supported by NIH grant R01EB018842. We gratefully acknowledge use of the Carl Zeiss Ultra FE-SEM at San Francisco State University for all SEM imaging. The FE-SEM and supporting facilities were obtained under NSF-MRI award no. 0821619 and NSF-EAR award no. 0949176. Confocal fluorescence imaging was conducted at the Nikon Imaging Center, UCSF. Nanostraw membrane fabrication was performed the Stanford Nano Shared Facilities. Remaining fabrication was performed at the UCSF Biomedical Micro & Nanotechnology Core and UC Berkeley Biomolecular Nanotechnology Center. The authors would like to thank Colin Zamecnik, Margaret Lowe, and Jessie Lee for providing mouse tissue for the ex vivo experiments. The authors declare no competing financial interest.
Funding AgencyGrant Number
NIH Predoctoral Fellowship5T32GM007175-37
Australian Research CouncilUNSPECIFIED
National Institute of Standards and Technology (NIST)70NANB15H192
NSF Graduate Research FellowshipDGE-1106400
NIH Predoctoral Fellowship5T32DK007762-38
NSF Graduate Research FellowshipDGE-114747
National Defense Science and Engineering Graduate (NDSEG) FellowshipUNSPECIFIED
Subject Keywords:microdevices, nanobiotechnology, nanostraws, nanowires, oral drug delivery
Issue or Number:6
Record Number:CaltechAUTHORS:20160802-105817297
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Official Citation:Fabrication of Sealed Nanostraw Microdevices for Oral Drug Delivery Cade B. Fox, Yuhong Cao, Cameron L. Nemeth, Hariharasudhan D. Chirra, Rachel W. Chevalier, Alexander M. Xu, Nicholas A. Melosh, and Tejal A. Desai ACS Nano 2016 10 (6), 5873-5881 DOI: 10.1021/acsnano.6b00809
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:69388
Deposited By: Tony Diaz
Deposited On:02 Aug 2016 18:08
Last Modified:11 Nov 2021 04:13

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