Formulation and characterisation of spray-dried o-carborane/ poly(vinylpyrrolidone) for boron neutron capture therapy of liver and lung cancer

Abstract

Boron neutron capture therapy (BNCT) is a non-conventional type of radio-chemotherapy that has been used to target a number of cancers, although predominantly brain tumours (gliomas). We report the co-spray-drying of o-carborane, as a model BNCT agent, with poly(vinylpyrrolidone) (PVP), a water-soluble polymer, to produce microparticle powders of high boron-content for BNCT treatment of liver and lung cancers. The powders have been characterised using NMR, particle sizing, electron microscopy and cytotoxicity tests. ¹H NMR indicated the high temperatures (180 °C) of the spray drying process did not degrade the PVP. Mean particle diameters (x₉₀) were in the 2–10 µm range, with finer fractions being present (x₁₀ @ 1–2 µm), and were therefore considered suitable size for delivery to the lungs. SEM imaging showed particles to be spherical, with dimples and cavities, caused by the spray drier nozzle characteristics, and similarly sized irregularly-shaped crystalline particles, thought to be o-carborane. Boron chemical mapping was attempted using EDS, although the low atomic weight of boron did not allow this to be possible. Cytotoxicity studies, using neoplastic (human glioblastoma U-87 MG) and non-neoplastic (human fetal lung fibroblast MRC-5) cells, revealed the PVP/o-carborane co-spray-dried particles to be non-toxic, as expected.