Researchers at the University of Nebraska–Lincoln have demonstrated that nesting specialized nanoparticles inside microparticles could protect engineered genes or virus-derived DNA against the rigors of the stomach and ensure safe passage to the intestine. Once there, the synthetic DNA could potentially enter cells to trigger the production of either disease-fighting proteins or antibodies essential to building immunity.

The investigators built the microparticles from a corn-based protein called zein and assembled the corresponding nanoparticles from chitosan, a derivative of the shells that house shrimp and other crustaceans. If further refined, this design could eventually help pills join the syringe as a delivery system for DNA, the team said.

Lead investigator Dr. Angela Pannier explained: “DNA can be easily and quickly synthesized, so once we identify the strain … we could go into the lab and within weeks have a vaccine mobilized. Right now, we have to produce [some] vaccines way in advance––usually six to 12 months out––given the time it takes to manufacture them.”

Pannier and her colleagues previously looked at whether a stand-alone zein microparticle could ferry DNA into the intestine. Although the particle maintained its integrity through the stomach, the enzymes of the intestine degraded it and left the DNA “just floating around,” Pannier said.

The combination of microparticles housing nanoparticles collectively protects DNA against the rigors of the stomach and intestine––an important step toward delivering vaccines and gene therapies in pill form.

According to Pannier, the team’s design boasts an overlooked but important advantage that should become more apparent as DNA vaccines become a reality.

“Other engineers in the field have made some pretty amazing, fantastic polymers that are highly complicated,” Pannier said. “But simple things are probably what are going to make it to the clinic––for scale-up, for production––so we’re [looking at] two highly abundant materials.”

Pannier envisions ingestible vaccines and gene therapies appealing to patients with a fear of needles. “If anyone’s ever been to the flu clinic with children…” she said.

The new research was published in the Journal of Controlled Release.

Source: University of Nebraska–Lincoln; April 11, 2017.

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