Harpinder Brar: Polymeric micelles for nose-to-brain delivery of crizotinib-IR786 in the treatment of glioblastoma
Glioblastoma (GBM) is one of the most challenging tumours to treat with limited treatment options. Tyrosine kinase inhibitors (TKIs) can target multiple pathways aberrantly activated in GBM; however, their clinical application is largely limited by their poor brain distribution and lack of tumour selectivity. Heptamethine cyanine dyes (HMCDs) have emerged as promising tumour-targeting agents and a conjugate of crizotinib (a TKI) with a HMCD IR-786 has been reported to have improved cytotoxic activity in GBM cells. The aim of this study is to formulate and characterise polymeric micelles to encapsulate crizotinib-IR786 conjugate for its nose-to-brain delivery in treatment of GBM. Size and zeta potential of the developed micelles was suitable for nose-to-brain delivery and the micelles had sufficient drug loading. Cytotoxicity studies revealed that crizotinb-IR786 micelles have comparable cytotoxicity to that of free crizotinib-IR786. Hence, the developed micelles have the potential to be used as suitable delivery vehicle for crizotinib-IR786.