The use of deoxycholic acid to enhance the oral bioavailability of biodegradable nanoparticles.
Oral delivery of nanoparticles encapsulating drugs and proteins remains a challenging route for administration due to the many barriers in the gastrointestinal tract that limit bioavailability. We hypothesized that bile salts could be used to improve the bioavailability of poly(lactide-co-glycolide) (PLGA) nanoparticles by protecting them during their transport through the gastrointestinal tract and enhancing their absorption by the intestinal epithelia. A deoxycholic acid emulsion is shown to protect PLGA nanoparticles from degradation in acidic conditions and enhance their permeability across a Caco-2 cell monolayer, an in vitro model of human epithelium. Oral administration of loaded PLGA nanoparticles to mice, using a deoxycholic acid emulsion, produced sustained levels of the encapsulant in the blood over 24-48 h with a relative bioavailability of 1.81. Encapsulant concentration was highest in the liver, demonstrating a novel means for targeted delivery to the liver by the oral route.
Samstein
Robert M
RM
Department of Biomedical Engineering, Yale University, 55 Prospect St., New Haven, CT 06511, USA.
Perica
Karlo
K
Balderrama
Fanor
F
Look
Michael
M
Fahmy
Tarek M
TM
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D003840:Deoxycholic Acid / Q000008:administration & dosage*; D006801:Humans; D019344:Lactic Acid / Q000493:pharmacokinetics*; D051379:Mice; D053758:Nanoparticles; D011100:Polyglycolic Acid / Q000493:pharmacokinetics*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000493:pharmacokinetics*
D011108:Polymers; D003840:Deoxycholic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid