Synthesis of novel N-vinylpyrrolidone/acrylic acid nanoparticles as drug delivery carriers of cisplatin to cancer cells

Abstract

This study aimed to synthesize novel polymeric nanoparticles (NPs) bound with cisplatin for the treatment of oral cancer. The NPs were synthesized from N-vinylpyrrolidone (NVP) and acrylic acid (AA) using 2 different methods based on a surfactant-free emulsion polymerization reaction. An azo initiator (V50) and bisacrylamide crosslinker were used in the reaction to create the NPs. The morphology, physicochemical characteristics, drug loading, and in vitro release were evaluated. Moreover, the cytotoxicity, death induction mechanism, and in vitro intracellular accumulation of cisplatin in HN22 cells were also investigated. Relatively spherical NPs with negative charge were obtained from both synthesis methods with the size in the range of 136–183 nm. The NPs were bound to cisplatin via coordination bond which was confirmed by FT-IR. The optimal NPs to cisplatin ratio was found to be 1:10 with %entrapment efficiency and loading capacity of 12–18% and 4 mmol/g, respectively. Approximately 47–83% of cisplatin was released from the NPs in 7 days in the presence of chloride ions depending on the pH of the release medium. The novel NPs from both methods were nontoxic to gingival fibroblast cells while the IC50 values of cisplatin-loaded NPs on HN22 cells were just above 20 μg/mL. In addition, the cisplatin-loaded NPs demonstrated a higher percentage in the early apoptotic death mechanism. Higher cellular deposition of cisplatin at the earlier period was obtained by the cisplatin-loaded NPs suggesting a slower but safer cancer-killing effect. Therefore, these novel NPs may be promising nanocarriers of cisplatin for oral cancer treatment.