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.