Selected Factors Affecting Oral Bioavailability of Nanoparticles Surface-Conjugated with Glycocholic Acid <i>via</i> Intestinal Lymphatic Pathway
Here, we describe the absorption pathways of nanoparticles whose surface is modified with bile acid and present environmental factors that influence oral bioavailability (BA) from the gastrointestinal tract (GIT). The approach utilized 100 nm sized fluorescence-labeled, carboxylated polystyrene nanoparticles (CPN) conjugated with glycocholic acid (G/CPN) to exclude potential artifacts, if existing, and instability issues in evaluating the transit of G/CPN in the GIT and measuring BA. The in vitro study using SK-BR-3 that expresses the apical sodium bile acid transporter showed that once G/CPN is internalized, it stayed 2.9 times longer in the cells than CPN, indirectly suggesting that G/CPN takes intracellular trafficking pathways different from CPN in SK-BR-3 cells. In a Caco-2 cell monolayer, G/CPN passed through the monolayer without damaging the tight junction. G/CPN, when administered orally in rodents, showed sustained transit time in the GIT for at least 4 h and was absorbed into the intestinal lymphatic system and circulated into the blood. Ingestion of food before and after oral administration delays G/CPN absorption and decreases BA. A decrease in gastrointestinal motility by anesthetic condition increased the relative BA of G/CPN by up to 74%. Thus, the oral BA of G/CPN can be optimized by taking food ingestion and gastrointestinal motility into account.
CITE THIS COLLECTION
Select your citation style and then place your mouse over the citation text to select it.
Kim, Kyoung Sub; Suzuki, Kenichi; Cho, Hana; Bae, You Han (2020): Selected Factors Affecting Oral Bioavailability of Nanoparticles Surface-Conjugated with Glycocholic Acid via Intestinal Lymphatic Pathway. ACS Publications. Collection. https://doi.org/10.1021/acs.molpharmaceut.0c00764
instability issuesCPNGIT4 hCaco -2 cell monolayertransit timefood ingestionSelected Factors Affecting Oral Bio...decreases BAanesthetic conditionmotilityapical sodium bile acid transporter2.9 timesIntestinal Lymphatic PathwayNanoparticles Surface-Conjugatedbile acidlymphatic systemglycocholic acidcarboxylated polystyrene nanoparticlesabsorption pathwaysSK-BR -3 cells100 nmintracellular trafficking pathwaysSK-BR -3