R. Hugh Daniels

Biomimetic nanowire coatings for next generation adhesive drug delivery systems

Without bioadhesive delivery devices, complex compounds are typically degraded or cleared from mucosal tissues by the mucous layer.While some chemically modified, microstructured surfaces have been studied in aqueous environments,adhesion due to geometry alone has not been investigated. Silicon nanowire-coated beads show significantly better adhesion than those with targeting agents under shear, and can increase the lift-off force 100-fold. We have shown that nanowire coatings, paired with epithelial physiology, significantly increase adhesion in mucosal conditions.

Break Free of the Matrix: Sensitive and Rapid Analysis of Small Molecules Using Nanostructured Surfaces and LDI-TOF Mass Spectrometry

We describe a novel nanostructured target plate for laser desorption/ionization (LDI) mass spectrometry, NALDI (Bruker Daltonics, Billerica, MA) target plates. The active surface comprises several layers of inorganic materials that are structured at the nanoscale and then further coated with a hydrophobic organic layer that facilitates sample deposition and LDI performance. These targets have been designed to analyze low mass (below 1500 Da), relatively polar, organic molecules and they have been shown to be up to 10 times more sensitive at detecting analytes in this range than conventional Matrix-assisted laser desorption/ionization—Time of Flight (MALDI)-TOF analysis. The targets can be used on standard LDI-TOF mass spectrometers and have been designed to fit the Bruker Flex series of mass spectrometers. This study demonstrates the utility of these targets for analyzing pharmaceutical compounds and demonstrates their superiority over conventional MALDI both in terms of performance and ease of use. Finally, we also demonstrate that these targets can be used in a unique sample preparation and analysis mode by allowing the capture and analysis of analytes from complex biological solutions.

Analysis of various organic and organometallic compounds using nanostructure-assisted laser desorption/ionization time-of-flight mass spectrometry (NALDI-TOFMS).

Nanostructure-assisted laser desorption/ionization time-of-flight mass spectrometry (NALDI-TOFMS) has been developed recently as a matrix-free/surface-assisted alternative to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). The NALDI surface of silicon nanowires is already very effective for the analysis of small to medium sized, polar organic molecules in positive ion mode. The current study examined this technology for the analysis of several nonpolar organic, organometallic, and ionic compounds in positive ion mode, as well as a fluorinated compound and various acids in negative ion mode. NALDI data are compared and contrasted with MALDI data for the same compounds, and the higher sensitivity of NALDI is highlighted by the successful characterization of two porphyrins for a sample amount of 10 amol per spot.

Hierarchical nanoengineered surfaces for enhanced cytoadhesion and drug delivery

Delivering therapeutics to mucosal tissues such as the nasal and gastrointestinal tracts is highly desirable due to ease of access and dense vasculature. However, the mucus layer effectively captures and removes most therapeutic macromolecules and devices. In previous work, we have shown that nanoengineered microparticles (NEMPs) adhere through the mucus layer, exhibiting up to 1000 times the pull-off force of an unmodified microsphere, and showing greater adhesion than some chemical targeting means. In this paper, we demonstrate that nanotopography improves device adhesion in vivo, increasing retention time up to ten-fold over unmodified devices. Moreover, we observe considerable adhesion in several cell lines using an in vitro shear flow model, indicating that this approach is promising for numerous tissues. We then demonstrate that nanowire-mediated adhesion is highly robust to variation in nanowire surface charge and cellular structure and function, and we characterize particle loading and elution. We present a form of cytoadhesion that utilizes the physical interaction of nanoengineered surfaces with subcellular structures to produce a robust and versatile cytoadhesive for drug delivery. These nanoscale adhesive mechanisms are also relevant to fields such as tissue engineering and wound healing because they likely affect stem cell differentiation, cell remodeling, migration, etc.

Effect of Nanofiber-Coated Surfaces on the Proliferation and Differentiation of Osteoprogenitors In Vitro

The osteoconductive property of titanium (Ti) surfaces is important in orthopedic and dental implant devices. Surface modifications of Ti have been proposed to further improve osseointegration. In this study, three different materials, silicon (Si), silicon oxide (SiO(2)), and titanium oxide (TiO(2)), were used to construct nanofibers for surface coating of Ti alloy Ti-6Al-4 V (Ti alloy). MC3T3-E1 osteoprogenitor cells were seeded on nanofiber-coated discs and cultured for 42 days. DNA, alkaline phosphatase, osteocalcin, and mineralization nodules were measured using PicoGreen, enzyme-linked immunosorbent assay, and calcein blue staining to detect the attachment, proliferation, differentiation, and mineralization of MC3T3-E1 cells, respectively. The results demonstrated that the initial cell attachments on nanofiber-coated discs were significantly lower, although cell proliferation on Si and SiO(2) nanofiber-coated discs was better than on Ti alloy surfaces. TiO(2) nanofibers facilitated a higher cellular differentiation capacity than Ti alloy and tissue culture-treated polystyrene surfaces. Thus, surface modification using nanofibers of various materials can alter the attachment, proliferation, and differentiation of osteoprogenitor cells in vitro.

Nanoengineered Surfaces Enhance Drug Loading and Adhesion

To circumvent the barriers encountered by macromolecules at the gastrointestinal mucosa, sufficient therapeutic macromolecules must be delivered in close proximity to cells.(1) Previously, we have shown that silicon nanowires penetrate the mucous layer and adhere directly to cells under high shear.(2) In this work, we characterize potential reservoirs and load macromolecules into interstitial space between nanowires. We show significant increases in loading capacity due to nanowires while retaining adhesion of loaded particles under high shear.