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].