Intestinal lymphatic transport study of antitumor lead compound T-OA with liposomes

Abstract

Intestinal lymphatic transport has been proved to have contribution to oral absorption of some highly lipophilic drugs. T-OA, 3βhydroxyolea-12-en-28-oic acid-3,5,6-trimethylpyrazin-2-methylester, has been reported to have anti-cancer activity. However， T-OA's poor solubility and difficulty to be absorbed cause low oral bioavailability. This work aims to investigate the influence of T-OA liposomes on intestinal lymphatic transport with rat model. T-OA liposomes were prepared by freeze-drying method, and particle size, zeta potential and entrapment efficiency of T-OA liposomes were detected to evaluate liposomes. Conscious restrained rat model was selected to evaluate intestinal lymphatic transport. The particle size, zeta potential and entrapment efficiency of T-OA liposomes were (184.05 ± 10.93) nm, (-21±0.85) mV and (93.24±2.25) %, respectively. The cumulative amounts in mesenteric lymph of T-OA liposomes and T-OA suspension within 12 h were (921.39±19.73) µg and (332.31±21.39) µg (n=6), respectively. Experimental results showed that T-OA liposomes could significantly promote T-OA’s intestinal lymphatic transport and enhance its oral bioavailability