Development of bozepinib-loaded nanocapsules for nose-to-brain delivery: preclinical evaluation in glioblastoma

Nanomedicine (Lond). 2021 Oct;16(23):2095-2115. doi: 10.2217/nnm-2021-0164. Epub 2021 Sep 15.

Abstract

Aim: To develop and characterize bozepinib-loaded lipid-core nanocapsules (BZP-LNC+) as a potential treatment for glioblastoma (GBM). Methods: Characterization of nanocapsules was performed by diameter, polydispersity index, Zeta potential, pH and encapsulation efficiency. GBM cell viability, cell cycle and Annexin/PI were evaluated after BZP-LNC+ treatment. Synergism between BZP-LNC+ and temozolomide (TMZ) was performed by CompuSyn software and confirmed in vitro and in vivo. Results: BZP-LNC+ showed adequate particle sizes, positive Zeta potential, narrow size distribution and high encapsulation efficiency. BZP-LNC+ reduces GBM growth by inducing apoptosis. BZP-LNC+ and TMZ showed synergistic effect in vitro and reduced the in vivo glioma growth by approximately 81%. Conclusion: The present study provides proof-of-principle insights for the combination of these drugs for GBM treatment.

Keywords: bozepinib; drug delivery; glioblastoma; intranasal; lipid-core nanocapsules; temozolomide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain
  • Cell Line, Tumor
  • Glioblastoma* / drug therapy
  • Humans
  • Nanocapsules* / therapeutic use
  • Oxazepines
  • Purines

Substances

  • 2,6-dichloro-9-(1-(p-nitrobenzenesulfonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl)-9H-purine
  • Nanocapsules
  • Oxazepines
  • Purines