Engineering Cobalt Bis(dicarbollide)-Loaded Polymeric Nanocarriers: From Controlled Fabrication to Drug Delivery for BNCT.

Poly(lactic-co-glycolic) acid nanoparticles (NPs) with the addition of the sodium salt of cobalt bis(1,2-dicarbollide) (COSAN) were developed for boron neutron capture therapy (BNCT). The Box-Behnken design was applied to predict an optimal value of variables and to obtain the desired NP characteristics. The optimized NPs had a size of 166 nm and a COSAN loading of 16%. Based on FTIR and UV-VIS spectrophotometry data, it was found that COSAN maintains chemical stability during the encapsulation process and exhibits prolonged release from NPs. A study of in vitro cytotoxicity and accumulation of the NPs on B16 cells revealed their low toxicity and high accumulation in cells after 24 h. In vivo analysis in B16-bearing BALB/c nude mice showed preliminary tumor-associated 10B distribution 12 h after iv administration of a deliberately low NP-CPPC dose (50 µg per mouse). The estimated intratumoral concentration was 0.31 µg 10B/g, which is below commonly cited BNCT delivery benchmarks. These results show high potential of the formulation, but require further optimization of dose, timing, biodistribution, normal-tissue exposure, tolerability and therapeutic-dose BNCT evaluation.