Ovarian carcinoma biological nanotherapy: Comparison of the advantages and drawbacks of lipid, polymeric, and hybrid nanoparticles for cisplatin delivery.

ABSTRACT

Ovarian carcinoma is one of the most common cancers among women. The most common type of ovarian cancer is epithelial ovarian cancer and cisplatin (DDP) is one of the most interesting chemotherapeutic drugs in clinical regimens for ovarian cancer. Nanoparticles (NPs) including lipid NPs, polymeric NPs, liposomes, dendrimers, oligomers, and nanotubes were usually used for anti-cancer drug delivery. In this study, DDP loaded nanostructured lipid carriers (DDP-NLC), polymeric NPs (DDP-PNP), and lipid-polymer hybrid nanoparticles (DDP-LPN) were prepared for the evaluation in vitro and in vivo. The efficiency of these three kinds of the NPs was compared in terms of in vitro drug release, cellular uptake, in vitro cell growth inhibition, in vivo pharmacokinetics, biodistribution and in vivo antitumor in mice. The size of DDP-PNP (119.8 nm) was smaller than DDP-NLC (132.4 nm) and DDP-LPN (141.2 nm). The release of DDP from DDP-NLC was faster than DDP-PNP. Cellular uptake efficiency of DDP-NLC and DDP-LPN was significantly higher than DDP-PNP. In vivo pharmacokinetics evaluation showed that plasma concentration - time curves (AUCs) of DDP-NLC, DDP-PNP, DDP-LPN and free DDP are 128, 210, 247, and 16 mg/L h, with T1/2 of 4.4, 5.1, 5.5, and 1.7 mg/L h. DDP-LPN exhibits the highest AUC and the longest T1/2. In vivo antitumor efficacy results investigated on ovarian cancer bearing BALB/c mice model demonstrated that DDP-LPN showed the strongest antitumor effect. In vitro and in vivo studies demonstrated that DDP-NLC, DDP-PNP and DDP-LPN have different advantages due to the various evaluations. The in vivo anti-tumor results indicate that DDP-LPN may have the best tumor inhibition ability. DDP-NLC, DDP-PNP, and DDP-LPN developed in this study could be used as promising strategies for the treatment of ovarian cancer according to different demands.