Single small molecule-assembled nanoparticles mediate efficient oral drug delivery

Oral drug delivery, which requires surviving the harsh environment in the gastrointestinal (GI) tract and penetrating the intestinal epithelium, has not been achieved using simple formulation nanoparticles (NPs). Medicinal natural products (MNPs) have been widely used in traditional medicine for disease management through oral consumption. However, most pharmacologically active compounds within MNPs do not have the properties suitable for oral applications. We hypothesize that some MNPs contain natural nanomaterials that can convert those compounds into oral formulations by forming NPs. After screening 66 MNPs, we identified five classes of small molecules that form NPs, many of which are capable of efficient drug encapsulation and GI penetration. We show that one of them, dehydrotrametenolic acid (DTA), is capable of mediating oral delivery for effective disease treatment. We determined that DTA NPs assemble through hydrogen bonding and penetrate the GI tract via apical sodium-dependent bile acid transporter. Our study reveals a novel class of single component, small molecule-assembled NPs for oral drug delivery, and suggests a novel approach to modernizing MNPs through nanomaterial discovery.