Role of surface charge in bioavailability and biodistribution of tri-block copolymernanoparticles in rats after oral exposure

Abstract

Tri-block copolymer nanoparticles (TCNP) are increasingly utilized, especially in drug delivery and diagnostics platforms. From in vitro studies, surface charge was observed to influence the transport of TCNP across the Caco-2 monolayers grown on transwell inserts. The objective of this study was to investigate the influence of surface charge on bioavailability and biodistribution of TCNP after oral exposure in vivo and to compare with the in vitro data. To attain the set objectives, monodisperse (45 ± 5 nm), fluorescent and differently charged (positive and negative) TCNP were orally administered to inbred Fischer 344 rats. Blood samples were collected at t = 0, 1/2, 1, 2, 4 and 6 h followed by sacrifice of the animals and collection of the major organs (lungs, liver, kidney, spleen, brain, intestine, and tibia). Quantitative assessments of TCNP in blood and organs were performed by fluorescence measurements. TCNP of both surface charges got absorbed and appeared in the blood within 1/2 h of oral administration. No significant difference in bioavailability and biodistribution could be found between positive and negative TCNP. Both the TCNP, irrespective of charge, showed major accumulation in the liver, kidneys and spleen, were detected in the brain and did not cause any significant increase in the serum alkaline phosphatase levels. Contrary to the in vitro data, surface charge was not found to influence the in vivo bioavailability and biodistribution of TCNP after oral exposure. The obtained results encourage further development of such TCNP, especially for drug delivery purposes.