Nanostructured Thin Film Eases Drug Delivery | Chemical & Engineering News
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Web Date: December 7, 2012

Nanostructured Thin Film Eases Drug Delivery

Nanomaterials: A new method allows large proteins to pass directly through epithelial tissue
Department: Science & Technology | Collection: Life Sciences
News Channels: Biological SCENE, Materials SCENE, Nano SCENE
Keywords: drug delivery, nanomaterials, nanotopography, nanostructured thin films
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Ruffling Cells
When researchers apply a nanostructured thin polymer film (black comb shape in cartoon, top) to a layer of epithelial cells, the junctions between cells loosen and ruffle (left). After the researchers remove the thin film, the cell junctions return to a normal, smooth architecture (right). Scale bar is 20 µm.
Credit: Nano Lett.
Illustration of effect of nanostructured surfaces on cell junctions.
 
Ruffling Cells
When researchers apply a nanostructured thin polymer film (black comb shape in cartoon, top) to a layer of epithelial cells, the junctions between cells loosen and ruffle (left). After the researchers remove the thin film, the cell junctions return to a normal, smooth architecture (right). Scale bar is 20 µm.
Credit: Nano Lett.

To take protein-based drugs, such as insulin or antibodies, patients must inject themselves—not an ideal method from the patients’ perspective. Unfortunately, pill forms of the drugs are not available because of the difficulty in getting the large molecules to pass through the tissue lining the gastrointestinal tract and into the bloodstream. Now, researchers have found that placing a nanostructured thin polymer film onto a layer of epithelial cells allows large proteins to slip through the tissue (Nano Lett., DOI: 10.1021/nl3037799).

Bioengineer Tejal Desai of the University of California, San Francisco, and her colleagues stumbled upon this phenomenon while studying how silicon nanowires on the surfaces of glass beads increased the beads’ adhesion to cells. They noticed that the modified beads also increased the amount of large molecules that passed through tissue. “We were getting these very large molecules to get across,” in ways that smooth particles didn’t allow, Desai says.

To study this effect more thoroughly, Desai and her colleagues decided to make raised patterns on thin films of polypropylene and test their effect on cells. Using silicon molds, they created films covered with carpets of tiny polymer pillars. They covered one film with 300-nm-long pillars, the other with 16-µm-long ones. They also made smooth films as a control.

The researchers placed the polymer films onto layers of human intestinal epithelial cells and measured the transport through the layers of three large proteins: immunoglobulin G, bovine serum albumin, and etanercept, which is an arthritis and psoriasis drug. Significantly more protein molecules of each type passed through the cell layer in contact with the film covered with short nanopillars than with the flat film or the film with longer pillars. For example, after two hours, the amount of drug that had crossed the cell layer was more than twice as high with the short-pillar film as with the flat or long-pillar films.

Using microscopy, the researchers observed that the junction between cells changed shape after coming into contact with the short nanopillar films. The scientists hypothesize that receptors on the cells’ surfaces that normally link up with other cells instead grab onto these nanopillars. This swap could disrupt the cell-to-cell connections, allowing space for the drugs to slip through. Only the short nanopillars seemed to have the stiffness necessary to mechanically stimulate the cells, Desai says.

Matthew Tirrell, director of the Institute for Molecular Engineering at the University of Chicago, says the nanostructured film method is a new way to make tissues permeable “that doesn’t require directly punching holes in the tissue.” Going around cells instead of going through them, he says, also avoids cellular machinery that can break down the drugs.

Samir Mitragotri, a chemical engineer at the University of California, Santa Barbara, thinks the study has profound implications not only for drug delivery, but also for understanding how the physical features of materials influence their biological interactions.

 
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