Polyborane encapsulated liposomes prepared using pH gradient and reverse-phase evaporation for boron neutron capture therapy: biodistribution in tumor-bearing mice

Various types of boron delivery for boron neutron capture therapy (BNCT) have been studied. To selectively destroy cancer cells, high accumulation and selective delivery of B-10 into tumor tissue are required. In this study, we developed polyboranes from 1,2-dicarba-closo-dodecaborane as boron carriers, and they were encapsulated into liposomes using either the pH gradient or reverse phase evaporation. The encapsulation efficiency of the liposome prepared using the pH gradient was twice as high as that prepared using reverse-phase evaporation. These liposomes, with diameters of either 50 or 100 nm, were injected into the tail veins of tumor-bearing mice to evaluate their biodistribution at 4, 12, and 24 h post-administration. Boron concentration of the polyborane encapsulated liposomes prepared using the pH gradient achieved 110-150 mu g/g of tumor tissue, and the liposomes prepared using the pH gradient were able to achieve an intratumoral B-10 concentration of 20-30 mu g/g without replacing B-11 with B-10. Moreover, this liposome maintained a high B-10 level in the tumor for at least 20 h. Average tumor/blood ratios of liposomes reached 5-15 at 4-24 h after injection. From these results, use of polyborane encapsulated liposomes prepared using the pH gradient for BNCT was suggested.