Triterpene-loaded microemulsion using Coix lacryma-jobi seed extract as oil phase for enhanced antitumor efficacy: preparation and in vivo evaluation

Int J Nanomedicine. 2014;9:109-19. doi: 10.2147/IJN.S54796. Epub 2013 Dec 19.

Abstract

Ganoderma lucidum triterpene-loaded microemulsions (TMEs) using Coix lacryma-jobi (adlay) seed oil as oil phase were prepared, characterized, and evaluated for enhanced antitumor activity. Ternary phase diagrams for the TMEs were constructed and the optimal preparation was developed. Transmission electron microscopy and dynamic light scattering showed that this formulation had a well defined spherical shape, a homogeneous distribution, a small size, and a narrow polydispersity index. The drug-loading rate was determined to be 9.87% by ultraviolet spectrophotometry, and acceptable stability under various stimulations in vitro was confirmed. Importantly, the TME formulation showed a significantly greater antiproliferative effect towards human lung carcinoma (A549) cells and murine lung tumor (Lewis) cells in comparison with suspension formulations containing triterpene and adlay seed oil as a positive control. The half-maximal inhibitory concentration of the TMEs was about 0.62 mg crude drug per mL, being 2.5-fold improved relative to that of the corresponding suspension formulation, but no significant cytotoxicity was observed for the bare microemulsion in A549 cells and Lewis cells. In vivo, the TME formulation showed markedly enhanced antitumor efficacy in a xenograft model of Lewis lung cancer after intragastric administration. Compared with cyclophosphamide, the TME formulation showed similar antitumor activity but less general toxicity. These results indicate the feasibility of using a microemulsion to increase the solubility of triterpene and adlay. TMEs hold promise as an efficient drug delivery system for the treatment of lung cancer.

Keywords: Ganoderma lucidum; adlay seed oil; lung cancer; microemulsion; triterpene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Cell Line, Tumor
  • Coix / chemistry*
  • Drug Compounding / methods
  • Drug Synergism
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / chemistry
  • Emulsions
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / pathology
  • Phase Transition
  • Phytotherapy / methods*
  • Plant Extracts / chemistry
  • Plant Extracts / therapeutic use*
  • Plant Oils / chemistry*
  • Seeds / chemistry*
  • Treatment Outcome
  • Triterpenes / administration & dosage*
  • Triterpenes / chemistry

Substances

  • Antineoplastic Agents
  • Drugs, Chinese Herbal
  • Emulsions
  • Plant Extracts
  • Plant Oils
  • Triterpenes