Harpinder Brar: Polymeric micelles for nose-to-brain delivery of crizotinib-IR786 in the treatment of glioblastoma

<p dir="ltr">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.</p>