Nanostructure-Mediated Transport of Biologics across Epithelial Tissue: Enhancing Permeability via Nanotopography

Abstract

Herein, we demonstrate that nanotopographical cues can be utilized to enable biologics >66 kDa to be transported across epithelial monolayers. When placed in contact with epithelial monolayers, nanostructured thin films loosen the epithelial barrier and allow for significantly increased transport of FITC-albumin, FITC-IgG, and a model therapeutic, etanercept. Our work highlights the potential to use drug delivery systems which incorporate nanotopography to increase the transport of biologics across epithelial tissue.

Nanotopography Facilitates in Vivo Transdermal Delivery of High Molecular Weight Therapeutics through an Integrin-Dependent Mechanism

“…12–15 In a recent study, Kam et al demonstrated that nanotopography loosens tight junctions in simple epithelia and dramatically increases transepithelial transport of etanercept, a high molecular weight therapeutic that is used clinically for rheumatoid arthritis (RA) and severe psoriasis and psoriatic arthritis. 16 However, the extent to which nanotopography loosens tight junctions in more stratified squamous epithelium such as skin or in vivo is not known.…”

Planar Bioadhesive Microdevices: A New Technology for Oral Drug Delivery

“…As microdevice design advances, future studies may apply a wide range of nanofabrication techniques to microdevice design as nanotopography has been shown to enhance muco- and cytoadhesion and interact with epithelial cells to enhance drug permeability [77–78]. However, resolutions below 100 nm are difficult to achieve with UV-based photolithography due to the diffraction limit of light [79].…”

“…Fabrication conditions have been altered to produce planar NEMPs, resulting in significant increases in drug uptake both in vitro and in vivo [76]. Nanostructured surfaces are also capable of loosening the epithelial barrier and providing increased permeability to protein therapeutics [78]. Therefore, incorporation of nanotopography into microdevices has potential to simultaneously increase device adhesion to the epithelial barrier and interact with epithelial cells to increase drug permeability, and studies regarding this concept are currently underway in our laboratory.…”

Selective three-dimensional hydrophilization of microstructured polymer surfaces through confined photocatalytic oxidation

“…The tailoring of the monomer chemical structure has inspired researchers to synthesize new polymeric materials with enhanced properties. However, for many applications, advanced surface properties, such as wettability [1], adhesion [2], permeability [3], are needed in addition to the special bulk properties. The microfluidic devices demand wettability control [1], cell culturing needs exceptional cell adherence with the surface [2], and drug delivery systems require permeability of the biomolecules within the body [3].…”

“…Therefore, the polymer surface modification attracts great interest of researchers. For example, it was found that a nanostructured thin film on contact with the epithelial tissue increases permeability of the proteins [3].…”