Self-assembled chitosan-sodium usnate drug delivery nanosystems: Synthesis, characterization, stability studies, in vitro cytotoxicity and in vivo biocompatibility against 143 B cells
Benedetta Brugnoli, Alessia Mariano, Beatrice Simonis, Cecilia Bombelli, Simona Sennato, Antonella Piozzi, Vincenzo Taresco, Veeren M. Chauhan, Steven M. Howdle, Anna Scotto d’Abusco, Iolanda Francolini
Abstract
Polymers are among the most studied materials as drug carriers, due to their tunable chemical structure and ability to self-assemble to give different types of nanostructures. In this study, chitosan (CS) nanoparticles (NPs) were investigated as carriers for the anticancer drug sodium usnate (NaU) for the treatment of osteosarcoma (OS) is the most prevalent primary malignant bone sarcoma in pediatric and adolescent patients. CS nano-assembling was induced by electrostatic interactions with the drug and the anionic cross-linker tripolyphosphate, thus obtaining stable nanosystems and a high drug encapsulation efficiency. Importantly, a reduction in NaU hepatotoxicity when encapsulated in CS NPs compared to free NaU was evidenced, suggesting that CS may have a protective role against liver damage. Unfortunately, NaU encapsulation also reduced drug toxicity versus osteosarcoma 143B cells compared to free NaU. Nevertheless, CS:NaU5x (0.312 mg/mL) was found to decrease 143B cells viability after 48 h and 72 h treatment without being hepatotoxic. Interestingly, this system also stimulated in 143B cells Maspin production, an agent known for its tumour suppressor properties. Relevant synergistic activity between chitosan and sodium usnate in promoting Maspin stimulation was found. That suggests the potential of the systems to reduce invasiveness of this type of cancer.