In many cases, oral administration is the preferred method of drug delivery, with formulation of nanoparticles shown to improve drug stability in the harsh gastrointestinal (GI) tract environment. However, diverse conditions in the GI tract, including varied pH, extensive mucus structure, and numerous cell types, are a proven barrier against effective oral delivery of nanoparticles. Now, a study from researchers at the University of Utah Health modifies nanoparticles to improve their uptake in the gastrointestinal tract. The team states their proof-of-concept involving orally administered nanoparticles could offer a new approach for common medications. The study is published online in the journal ACS Nano.
Previous studies show nanomedicine is a burgeoning field involving the delivery of tiny particles, or nanoparticles, to carry drugs to treat a variety of conditions, including cancer. However, nanoparticles usually have to be injected into the bloodstream due to the fact they aren’t absorbed well orally. The current study provides a proof-of-concept for a nanoparticle oral delivery system and proposes pathways for oral nanoparticle absorption in the GI.
The current study modifies the surface of the nanoparticles with glycocholic acid, a bile acid known to help the body absorb fat in the small intestine. To monitor the nanoparticle movement, the researchers affixed a red fluorescence tag on the treated particles and watched as they circulated through the body. Results show glycocholic acid acts like a cloak, allowing the nanoparticle to slip incognito through the lining of the small intestine. Data findings show the coating helps the nanoparticles bind to proteins allowing them to move into the gut’s lymphatic system where it can access the bloodstream.
Results show when the team fed the modified nanoparticles to rats, approximately forty-seven percent of the particles made it into the blood, as opposed to the 7% seen for nanoparticles lacking bile acids. Data findings show bile acids on the nanoparticles interact with a bile acid transporter found on the surface of enterocytes, possibly helping the nanoparticles move through the cells and into the blood system. The lab notes it takes about one to ten hours for the nanoparticles to appear in the bloodstream.
The team surmises their study proposes a pathway for oral nanoparticle absorption via the GI lymphatic system, utilizing apical bile acid transporter-mediated cellular uptake. For the future, the researchers state this work is still at the preliminary stages with more research needed to move the results from animal studies to clinical trials.
Source: University of Utah Health
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