Optimized synthesis of glycyrrhetinic acid-modified chitosan 5-fluorouracil nanoparticles and their characteristics.
The nanoparticle drug delivery system, which uses natural or synthetic polymeric material as a carrier to deliver drugs to targeted tissues, has a broad prospect for clinical application for its targeting, slow-release, and biodegradable properties. Here, we used chitosan (CTS) and hepatoma cell-specific binding molecule glycyrrhetinic acid to synthesize glycyrrhetinic acid-modified chitosan (GA-CTS). The synthetic product was confirmed by infrared (IR) spectra and hydrogen-1 nuclear magnetic resonance. The GA-CTS/5-fluorouracil (5-FU) nanoparticles were synthesized by combining GA-CTS and 5-FU and conjugating 5-FU onto the GA-CTS nanomaterial. The central composite design was performed to optimize the preparation process as CTS:tripolyphosphate sodium (TPP) weight ratio =5:1, 5-FU:CTS weight ratio =1:1, TPP concentration =0.05% (w/v), and cross-link time =50 minutes. GA-CTS/5-FU nanoparticles had a mean particle size of 193.7 nm, a polydispersity index of 0.003, a zeta potential of +27.4 mV, and a drug loading of 1.56%. The GA-CTS/5-FU nanoparticle had a protective effect on the drug against plasma degrading enzyme, and provided a sustained release system comprising three distinct phases of quick, steady, and slow release. Our study showed that the peak time, half-life time, mean residence time and area under the curve of GA-CTS/5-FU were longer or more than those of the 5-FU group, but the maximum concentration (C(max)) was lower. We demonstrated that the nanoparticles accumulated in the liver and have significantly inhibited tumor growth in an orthotropic liver cancer mouse model.
Department of General Surgery, Shanghai, People's Republic of China ; Department of Endoscopy, Pudong New Area District Zhoupu Hospital, Shanghai, People's Republic of China.
Mingrong
M
Cheng
Zhejiang Huafon Fiber Research Institute, Zhejiang Huafon Spandex Co, Ltd, Wenzhou, People's Republic of China.
Houxiang
H
Chen
School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, People's Republic of China.
Yong
Y
Wang
Department of General Surgery, Shanghai Fifth People's Hospital, Fudan University, Shanghai, People's Republic of China.
Hongzhi
H
Xu
Department of General Surgery, Shanghai Fifth People's Hospital, Fudan University, Shanghai, People's Republic of China.
Bing
B
He
Department of General Surgery, Shanghai, People's Republic of China.
Jiang
J
Han
Department of General Surgery, Shanghai, People's Republic of China.
Zhiping
Z
Zhang
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D004058:Diffusion; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000737:chemistry*; D006034:Glycyrrhetinic Acid / Q000737:chemistry*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D053769:Nanocapsules; D048271:Chitosan; D006034:Glycyrrhetinic Acid; D005472:Fluorouracil
chemotherapy; liver cancer; pharmacokinetics efficacy; targeted therapy