Pluronic F127-based micelles for tumor-targeted bufalin delivery.

Abstract

In this study, we developed novel thermal and redox-responsive micelles based on the Pluronic F127 tri-block copolymer and employed these for redox-responsive intratumor release of bufalin, an anti-cancer drug. Pluronic F127 was first functionalized with carboxylate groups, and then assembled into micelles. The HOOC-F127-COOH micelles are 20 ± 4 nm in size at 37 °C, but expand to 281 ± 5 nm when cooled to 4 °C. This allows for the free diffusion of bufalin into the micellar cores at low temperatures, while at 37 °C the micelles are much more compact and the drug molecules can be effectively held in their interiors. A high encapsulation efficiency and loading content were obtained via drug incorporation at 4 °C. The drug-loaded micelles were cross-linked with cystamine, which contains a disulfide bond responsive to the local cancer microenvironment. In vitro studies showed that drug release from the cross-linked micelles was low under normal physiological conditions, but markedly accelerated upon exposure to conditions representative of the intracellular tumor environment. Confocal microscopy revealed that the cross-linked micelles gave high levels of drug release inside the cells. In vivo studies in mice showed the drug-loaded cross-linked micelles have potent anti-tumor activity, leading to high levels of apoptosis of tumor cells and significant reductions in tumor volume. The drug-loaded cross-linked micelles did not significantly influence body weight, and there was no evidence for detrimental off-target effects. These results indicate that the Pluronic-based micelles developed in this work are promising drug delivery systems for the targeted treatment of cancer.

• Authors: Haijun Wang, Gareth R Williams, Jianrong Wu, Junzi Wu, Shiwei Niu, Xiaotian Xie, Shude Li, Li-Min Zhu
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 559 Pg. 289-298 (Mar 25 2019) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 30707933 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Bufanolides
• Disulfides
• Drug Carriers
• Micelles
• Polymers
• Poloxamer
• Cystamine
• bufalin

Topics

• Animals
• Apoptosis (drug effects)
• Bufanolides (administration & dosage, chemistry)
• Cell Line
• Cell Line, Tumor
• Cystamine (chemistry)
• Disulfides (chemistry)
• Drug Carriers (chemistry)
• Drug Delivery Systems (methods)
• Drug Liberation
• Female
• Mice
• Mice, Inbred ICR
• Micelles
• Particle Size
• Poloxamer (chemistry)
• Polymers (chemistry)
• Tumor Microenvironment (drug effects)