Oral nanoparticles show promise in animal model

Last Updated: 2018-08-13

By Will Boggs MD

NEW YORK (Reuters Health) - Oral nanoparticles are efficiently absorbed by the gut and transported into systemic circulation, researchers report.

"In particular, the nanoparticles move to systemic circulation via gut associated lymphoid tissue (GALT) instead of the portal system," Dr. You Han Bae of the University of Utah, in Salt Lake City, told Reuters Health by email. "This allows to avoid hepatic first-pass effect and free accessibility to the main lymphatic system (mesenteric lymph node, cisterna chyli, and thoracic duct) where the majority of lymphatic cells reside."

Previous studies of nanoparticles have relied mainly on intravenous administration, because oral insoluble nanoparticles have shown limited absorption in the intestine.

Dr. Bae and colleagues conjugated glycocholic acid (GCA) to the surface of carboxylated polystyrene spherical nanoparticles (CPN) and tested the resulting nanoparticles in vitro and in a rat model.

Nanoparticles measuring 100 and 250 nm in diameter were stable in water and in simulated gastric and intestinal fluids, whereas smaller particles showed limited degrees of aggregation.

After oral dosing, the bioavailability of 100-nm nanoparticles was 47% at 1 mg/kg in 0.5 mL sterile water, 40% at 5 mg/kg, 47% at 10 mg/kg and 38% at 20 mg/kg (P>0.1), the researchers report in ACS Nano, online August 8.

Oral bioavailability increased with increasing density of GCA on the CPN surface and decreased with overall nanoparticle size.

Once absorbed, nanoparticles were transported to the systemic circulation by way of the rat lymphatic system, evidently sharing the chylomicrons transport pathways.

"The nanocarrier can carry a broad range of active pharmaceutical ingredients by design, such as proteins/peptides, genetic materials, and small molecules, which cannot be orally dosed by traditional medication technologies," Dr. Bae said. "We are actively developing practical dosage forms of peptide drugs, such as insulin and exenatide, and small molecule anticancer drugs, such as doxorubicin and docetaxel."

Dr. Bae is also Chief Science Officer of Ileo Science, the company he founded to commercialize this technology.

SOURCE: https://bit.ly/2nzvvTX

ACS Nano 2018.