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A robust nanofluidic membrane with tunable zero-order release for implantable dose specific drug delivery

Daniel H. FineDepartment of Nanomedicine and Biomedical Engineering, The University of Texas Health Science Center at Houston, Houston, TX 77030, USAAlessandro GrattoniDepartment of Nanomedicine and Biomedical Engineering, The University of Texas Health Science Center at Houston, Houston, TX, USASharath HosaliNanomedical Systems, Inc., Austin, TX, USAArtūras ŽiemysDepartment of Nanomedicine and Biomedical Engineering, The University of Texas Health Science Center at Houston, Houston, TX, USAEnrica De RosaDepartment of Nanomedicine and Biomedical Engineering, The University of Texas Health Science Center at Houston, Houston, TX, USAJaskaran GillDepartment of Nanomedicine and Biomedical Engineering, The University of Texas Health Science Center at Houston, Houston, TX, USARyan MedemaNanomedical Systems, Inc., Austin, TX, USAHudson LeeNanomedical Systems, Inc., Austin, TX, USAMiloš KojićDepartment of Nanomedicine and Biomedical Engineering, The University of Texas Health Science Center at Houston, Houston, TX, USAMiljan MiloševićR & D Center for Bioengineering, Sretenjskog Ustava, Serbia KragujevacLouis BrousseauDepartment of Nanomedicine and Biomedical Engineering, The University of Texas Health Science Center at Houston, Houston, TX, USARandy GoodallNanomedical Systems, Inc., Austin, TX, USAMauro FerrariDepartment of Nanomedicine and Biomedical Engineering, The University of Texas Health Science Center at Houston, Houston, TX, USAXuewu LiuDepartment of Nanomedicine and Biomedical Engineering, The University of Texas Health Science Center at Houston, Houston, TX, USA

2010en

ABI

Annotatsiya

This manuscript demonstrates a mechanically robust implantable nanofluidic membrane capable of tunable long-term zero-order release of therapeutic agents in ranges relevant for clinical applications. The membrane, with nanochannels as small as 5 nm, allows for the independent control of both dosage and mechanical strength through the integration of high-density short nanochannels parallel to the membrane surface with perpendicular micro- and macrochannels for interfacing with the ambient solutions. These nanofluidic membranes are created using precision silicon fabrication techniques on silicon-on-insulator substrates enabling exquisite control over the monodispersed nanochannel dimensions and surface roughness. Zero-order release of analytes is achieved by exploiting molecule to surface interactions which dominate diffusive transport when fluids are confined to the nanoscale. In this study we investigate the nanofluidic membrane performance using custom diffusion and gas testing apparatuses to quantify molecular release rate and process uniformity as well as mechanical strength using a gas based burst test. The kinetics of the constrained zero-order release is probed with molecules presenting a range of sizes, charge states, and structural conformations. Finally, an optimal ratio of the molecular hydrodynamic diameter to the nanochannel dimension is determined to assure zero-order release for each tested molecule.

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DOI: 10.1039/c0lc00013b

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