Celastrol-conjugated chitosan oligosaccharide for the treatment of pancreatic cancer

Drug Deliv. 2022 Dec;29(1):89-98. doi: 10.1080/10717544.2021.2018521.

Abstract

Celastrol is a promising antitumor drug candidate, but the poor water solubility and cytotoxicity limit its clinical application. Herein, we synthesized a Celastrol (Cel)-chitosan oligosaccharide (CSO) conjugate (Cel-CSO) for drug delivery. Celastrol was conjugated to a CSO backbone via amide bond formation, which was verified by infrared spectrum (IR) analyses. The Cel-CSO contained ∼10 wt% of Celastrol showed excellent aqueous solubility (18.6 mg/mL) in comparation with the parent Celastrol. Cel-CSO significantly inhibited tumor growth, induced apoptosis, and effectively suppressed tumor metastasis in human pancreatic cancer cells (BxPC-3). While the cytotoxicity of Cel-CSO in hepatic cells (HL7702) was lower than that of the free Celastrol. Cel-CSO enhanced the anticancer efficacy, promoted the circulation time of Celastrol, and reduced the subacute toxicity, which indicated that CSO can be a promising Celastrol delivery system for pancreatic cancer therapy.

Keywords: Celastrol; Chitosan oligosaccharide; drug delivery system; pancreatic cancer; toxicity.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chemistry, Pharmaceutical
  • Chitosan / chemistry*
  • Drug Liberation
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Oligosaccharides / chemistry
  • Pancreatic Neoplasms / pathology*
  • Particle Size
  • Pentacyclic Triterpenes / administration & dosage
  • Pentacyclic Triterpenes / pharmacology*
  • Solubility
  • Tumor Burden / drug effects

Substances

  • Antineoplastic Agents
  • Oligosaccharides
  • Pentacyclic Triterpenes
  • Chitosan
  • celastrol

Grants and funding

This project was sponsored by National Natural Science Foundation of China [21601053, U1604185], Henan Scientific and technological Innovation Talents Project [20HASTIT050], Henan Science Fund for Excellent Young Scholars [212300410057], the Scientific and Technological Brainstorm Project of Henan Province [202102310515], Innovative Research Team in Science and Technology of Henan Province [211RTSTHN026], Leading Talents Project of Science and Technology Innovation in Central Plains [204200510021].