Intraperitoneal administration of biocompatible hyaluronic acid hydrogel containing multi-chemotherapeutic agents for treatment of colorectal peritoneal carcinomatosis

Int J Biol Macromol. 2020 Jun 1:152:718-726. doi: 10.1016/j.ijbiomac.2020.02.326. Epub 2020 Feb 29.

Abstract

Colorectal peritoneal carcinomatosis (CRPC) is an advanced stage of colorectal cancer (CRC), which significantly decreases patient survival and quality of life. Here, the naturally occurring polysaccharide hyaluronic acid (HA) was used to prepare an injectable hydrogel and simultaneously deliver 5-fluorouracil (5-FU), cisplatin (DDP) and paclitaxel (PTX) microspheres for intraperitoneal CRPC chemotherapy. The drug-loaded HA hydrogel released the drugs in a sustained manner, and showed low toxicity both in vitro and in a mouse model of CRPC. Furthermore, direct injection of the drug-loaded HA hydrogel in the abdominal cavity of tumor-bearing mice significantly decreased tumor growth and liver/lung metastasis, along with decreasing the volume of ascites and inhibiting local intestinal infiltration of the tumor cells. Therefore, this novel multi-drug hydrogel delivery system may effectively clear CRPC tumors without any adverse effects when used in intraperitoneal chemotherapy.

Keywords: Cisplatin; Colorectal peritoneal carcinomatosis; Hyaluronic acid; Hydrogel; Microsphere; Paclitaxel.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Biocompatible Materials / chemistry*
  • Carcinoma / drug therapy*
  • Cell Line, Tumor
  • Colorectal Neoplasms / drug therapy*
  • Drug Delivery Systems / methods
  • Female
  • Humans
  • Hyaluronic Acid / administration & dosage*
  • Hydrogels / administration & dosage*
  • Injections, Intraperitoneal / methods
  • Liver Neoplasms / drug therapy
  • Lung Neoplasms / drug therapy
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Peritoneal Neoplasms / drug therapy*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Antineoplastic Agents
  • Biocompatible Materials
  • Hydrogels
  • Hyaluronic Acid