Central nervous system (CNS)
metastasis is one of the serious complications of
epidermal growth factor receptor (EGFR)-mutant
lung cancer, which arises due to poor penetration of the brain-blood barrier by EGFR-
tyrosine kinase inhibitors (EGFR-TKIs). Although
osimertinib, a third-generation EGFR-TKI, has efficacy against CNS
metastases, further treatment modalities are still needed as some of these lesions do not respond to
osimertinib, or undergo progression after an initial response to this
drug if
radiotherapy has already been conducted. Here, we investigated the efficacy of water-soluble
erlotinib (NUFS-sErt) against these
metastases. This agent was synthesized using a nano-particulation platform technology utilizing fat and supercritical fluid (NUFS™) to resolve the low solubility problem that typically prevents the creation of
injectable forms of EGFR-TKIs. The average NUFS-sErt particle size was 236.4 nm, and it showed time-dependent dissolution in
culture media. The effects of NUFS-sErt were similar to those of conventional
erlotinib in terms of inhibiting the proliferation of EGFR-mutant
lung cancer cells and suppressing EGFR signaling. In an intraperitoneal xenograft model of HCC827 cells, intraperitoneal administration of NUFS-sErt produced a dose-dependent inhibition of
tumor growth and enhanced survival rate. Notably, the injection of NUFS-sErt into the brain ventricle caused significant
tumor growth inhibition in an intracranial xenograft model. Hence, our current findings indicate that NUFS-sErt is a novel, water-soluble form of
erlotinib that can be administered using intraventricular or
intrathecal injections. The target cases would be patients with a progressive CNS
metastasis and no other therapeutic options. This
drug could also be given intravenously to patients with swallowing difficulties or an inability to ingest due to a medical condition.