Silicon Nanowires for Bioadhesion and Drug Delivery
- Author(s): Fischer, Kathleen Elizabeth
- Advisor(s): Desai, Tejal A
- et al.
Mucosal tissues have great potential for delivery of therapeutic macromolecules, but drug absorption is often thwarted by chemical and physical barriers, such as the mucus layer. Although mucoadhesive technologies increase gastrointestinal residence time, many macromolecules are subjected to degradation or clearance within the mucus layer. Recent advances in nanotechnology have allowed for the fabrication of silicon nanowires on microparticles in a conformal three-dimensional coating. These nanowire coatings have been shown to be robust in acid and to degrade on the scale of weeks in physiological solutions.
Nanowire-coated microparticles interact with nanoscale cellular features, such as microvilli, allowing of increased surface area of contact. These devices adhere strongly under harsh physiological conditions, such as shear of over 100 dynes/cm2, a model mucus layer, and various insults to the cellular cytoskeleton. Because they adhere by geometry-dependent mechanisms and interact directly with the epithelial cells, they are retained better than mucoadhesives and adhere well to several types of tissue. Under tensile force, the nanowire- coated devices adhere up to 1000-fold stronger than the equivalent uncoated devices. Overall, charge and nanowire geometry are most influential in nanowire-related adhesion, indicating that surface area dependent forces are involved. The in vitro adhesion results have been validated in two separate animal models: the mouse and the dog. In beagles, nanowire- coated stainless steel particles were retained in the stomach at least ten times longer than similar controls. In mice, nanowire-coated microspheres remained in the stomach until at least 5 hours after dosing.
Furthermore, the nanowire coating on these devices offers a convenient reservoir, where macromolecules may be loaded. Because the therapeutics eventually encase all of the nanowires, a trade-off is made between loading capacity and adhesion. However, by loading controlled pore glass particles, adhesion may be retained and/or enhanced. In addition to the initial surface area adhesion, nanowire coatings induce cellular remodeling, though they are not internalized. Overall, these nanowires show low toxicity in Caco-2 cells and do not induce inflammation in vitro.
Thus, nanowire coatings show promise for resolving some of the most difficult oral delivery barriers, such as penetrating the mucus layer, adhering directly to cells, and increasing residence time in close proximity to the gastrointestinal epithelial cells. In vitro adhesion studies have been validated in vivo, and nanowires have been demonstrated to be biocompatible in vitro. By integrating nano- and microscale functionalities, nanowire-coated devices reap the benefits of both size scales, and show promise for application to a variety of therapeutic systems.