Colon-specific microspheres loaded with puerarin reduce tumorigenesis and metastasis in colitis-associated colorectal cancer

Int J Pharm. 2019 Oct 30;570:118644. doi: 10.1016/j.ijpharm.2019.118644. Epub 2019 Aug 26.


Colitis-associated colorectal cancer (CAC) is a common malignancy that develops in chronically inflamed mucosa and is usually accompanied by metastases at other sites. Puerarin, a natural isoflavone isolated from the root of the Pueraria lobata (Willd.) Ohwi, has potential anti-colon cancer activity. However, the poor solubility and low bioavailability of puerarin has restricted its application in the pharmaceutical industry. In the present study, pH-responsive alginate microspheres loaded with puerarin were prepared by emulsification/internal gelation for targeted treatment of colitis-associated colorectal cancer. Herein, puerarin, as an active drug, could participate in the construction of alginate microspheres with hydrogen bonding. The microspheres exhibited pH-responsive release behavior with little release of puerarin in simulated gastric fluid and high amounts (approximately 55%) of release in simulated colonic fluid. A fluorescence tracer indicated microspheres had high retention time of more than 20 h in the colon. Meanwhile, puerarin-loaded alginate microspheres not only significantly decreased the inflammatory response by downregulating the levels of pro-tumorigenic cytokines, but they reduced tumorigenesis and metastasis by inhibiting epithelial-mesenchymal transitions in AOM/DSS-induced colitis-associated colorectal cancer in mice. The overall results suggested that puerarin-loaded alginate microspheres could effectively inhibit development of colonic tumors, which could be developed as a promising therapeutic strategy for colitis-associated colorectal cancer.

Keywords: Colitis-associated colorectal cancer; Colon-specific drug delivery; Microspheres; Puerarin; pH-responsive.

MeSH terms

  • Alginates / chemistry
  • Animals
  • Body Fluids / drug effects
  • Carcinogenesis / drug effects*
  • Colitis / complications*
  • Colon / drug effects*
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / etiology*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / etiology*
  • Down-Regulation / drug effects
  • Epithelial-Mesenchymal Transition / drug effects
  • Hydrogen Bonding
  • Hydrogen-Ion Concentration
  • Inflammation / drug therapy
  • Intestinal Mucosa / drug effects
  • Isoflavones / chemistry
  • Isoflavones / pharmacology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microspheres


  • Alginates
  • Isoflavones
  • puerarin