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

Pak J Pharm Sci. 2020 Mar;33(2):631-640.

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.

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / metabolism*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Intestinal Absorption / drug effects
  • Intestinal Absorption / physiology*
  • Liposomes
  • Lymphatic Vessels / drug effects
  • Lymphatic Vessels / metabolism*
  • Male
  • Oleanolic Acid / chemistry
  • Oleanolic Acid / metabolism*
  • Oleanolic Acid / pharmacology
  • Pyrazines / chemistry
  • Pyrazines / metabolism*
  • Pyrazines / pharmacology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Antineoplastic Agents, Phytogenic
  • Liposomes
  • Pyrazines
  • Oleanolic Acid
  • tetramethylpyrazine