Chitosan/Sulfobutylether-β-Cyclodextrin Nanoparticles for Ibrutinib Delivery: A Potential Nanoformulation of Novel Kinase Inhibitor

J Pharm Sci. 2020 Feb;109(2):1136-1144. doi: 10.1016/j.xphs.2019.10.007. Epub 2019 Oct 10.

Abstract

In this study, a novel Bruton's tyrosine kinase inhibitor, ibrutinib, was loaded into chitosan/sulfobutylether-β-cyclodextrin nanoparticles (NPs). NPs have gained high loading efficiency for the hydrophobic drug due to the inclusion of cyclodextrin. Ibrutinib-loaded NPs with an average diameter of 277.9 nm and ζ-potential of +19.1 mV were obtained after regulating several influencing factors. Electrostatic reaction between mucin and NPs indicated that the NPs had a mucoadhesive property. Kinase catalytic phosphorylation was monitored by capillary zone electrophoresis and found that chitosan/sulfobutylether-β-cyclodextrin NPs did not weaken ibrutinib activity on the target kinase. In vitro drug release studies revealed that ibrutinib-loaded NPs exhibited a significantly slower gastric-release rate. This study applied a feasible nanocarrier for ibrutinib delivery, and the potential nanoformulation maintains drug activity and shows a sustained release property. These outcomes are helpful for the formulation exploitation of tyrosine kinase inhibitors.

Keywords: chitosan; ibrutinib; nanoformulation; nanoparticle; sulfobutylether-β-cyclodextrin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Chitosan*
  • Drug Carriers
  • Nanoparticles*
  • Particle Size
  • Piperidines
  • Protein Kinase Inhibitors
  • beta-Cyclodextrins

Substances

  • Drug Carriers
  • Piperidines
  • Protein Kinase Inhibitors
  • beta-Cyclodextrins
  • ibrutinib
  • SBE4-beta-cyclodextrin
  • Chitosan
  • Adenine