Abstract
In this study, novel liver targeted doxorubicin (DOX) loaded alginate (ALG) nanoparticles were prepared by CaCl2 crosslinking method. Glycyrrhetinic acid (GA, a liver targeted molecule) modified alginate (GA-ALG) was synthesized in a heterogeneous system, and the structure of GA-ALG and the substitution degree of GA were analyzed by 1H NMR, FT-IR and elemental analysis. The drug release profile under the simulated physiological condition and cytotoxicity experiments of drug-loaded GA-ALG nanoparticles were carried out in vitro. Transmission electron micrographs (TEM) and dynamic light scattering (DLS) analysis showed that drug-loaded GA-ALG nanoparticles have spherical shape structure with the mean hydrodynamic diameter around 214 ± 11 nm. The drug release was shown to last 20 days, and the MTT assay suggested that drug-loaded GA-ALG nanoparticles had a distinct killing effect on 7703 hepatocellular carcinoma cells.
Similar content being viewed by others
References
Ehrlich P. Collected studies on immunity. New York: Pergamon Press, 1906. 442–447
Wang X, Yang L L, Chen Z, Shin D M. Application of nanotechnology in cancer therapy and imaging. CA Cancer J Clin, 2008, 58: 97–110
Shinoda T, Maeda A, Kojima S, Kagatani S, Konnoet Y. Nanosphere coated with lactosyl-polystyrene polymer as a targeting carrier to hepatocytes. Drug Deliv, 1999, 6: 147–151
Sun J B, Duan J H, Dai S L, Ren J, Zhang Y D, Tian J S, Li Y. In vitro and in vivo antitumor effects of doxorubicin loaded with bacterial magnetosomes (DBMs) on H22 cells: The magnetic bio-nanoparticles as drug carriers. Cancer Lett, 2007, 258: 109–117
Gao S Y, Chen J N, Xu X R, Ding Z, Yang Y H, Hua Z C, Zhang Z F. Galactosylated low molecular weight chitosan as DNA carrier for hepatocyte-targeting. Int J Pharm, 2003, 255: 57–68
Hong G B, Yuan R X, Liang B L, Shen J, Yang X Q, Shuai X T. Folate-functionalized polymeric micelle as hepatic carcinomatargeted, MRI-ultrasensitive delivery system of antitumor drugs. Biomed Microdevices, 2008, 10: 693–700
Negishi M, Irie A, Nagata N, Ichikawa A. Specific binding of glycyrrhetinic acid to the rat liver membrane. Biochim Biophys Acta, 1991, 1066: 77–82
Gu Y T, Zhou F C, Yang S M, Zhang J X, Jin S, Cheng L Z. Effects and binding sites of glycyrrhetinic acid and glycyrrhizin on isolated rat hepatocyte membrane. J Shanghai Med (in Chinese), 2000, 27: 270–273
Yang S M, Zhou F C, Gu Y T, Liu S T, Jiang X L, Cheng L Z. Respective of the receptors for glycyrrhetinic and for glycyrrhizin on isolated hepatocyte membranes. Chin J Hepatol (in Chinese), 1999, 7: 27–29
Mao S J, Hou S X, Jin H, Zhang L K, Jiang B. Preparation of liposomes surface-modified with glycyrrhetinic acid targeting to hepatocytes. Chin J Chin Mater Med (in Chinese), 2003, 28:328–331
Mao S J, Bi Y Q, Jin H, Wei D P, He R, Hou S X. Preparation, characterization and uptake by primary cultured rat hepatocytes of liposomes surface-modified with glycyrrhetinic acid. Pharmazie, 2007, 62: 614–619
Cha R T, Du T, Yuan Z. Syntheses and characterization of poly(γ-benzyl-L-glutamate) containing liver targeting group in main chain. Chem J Chin U (in Chinese), 2006, 27: 885–887
Cha R T, He X T, Du T, Yuan Z. Synthesis and characterization of chitosan nanoparticles modified by glycyrrhetinic acid as a liver targeting drug carrier. Chem J Chin U (in Chinese), 2007, 28: 1098–1100
Tian Q, Wang W, He X T, Zhu X C, Huang W, Zhang C N, Yuan Z, Chen X S. Glycyrrhetinic acid-modified nanoparticles for drug delivery: preparation and characterization. Chinese Sci Bull (accepted)
Pranee L, Khanittha N, Nutthapon J, Pornchai R, Ubonthip N. Preparation of alginate nanocapsules containing turmeric oil. Carbohyd Polym, 2008, 74: 209–214
Yu C Y, Jia L H, Yin B C, Zhang X Z, Cheng S X, Zhuo R X. Fabrication of nanospheres and vesicles as drug carriers by self-assembly of alginate. J Phys Chem C, 2008, 112: 16774–16778
Hee D H, Aeri L, Chung K S, Taewon H, Hasoo S, Chong O L, Byung C S. In vivo distribution and antitumor activity of hepa-rin-stabilized doxorubicin-loaded liposomes. Inter J Pharm, 2006, 313: 181–188
Zhao M D, Hu F Q, Du Y Z, Yuan H, Chen F Y, Lou Y M, Yu H Y. Coadministration of glycolipid-like micelles loading cytotoxic drug with different action site for efficient cancer chemotherapy. Nanotechnology, 2009, doi:10.1088/0957-4484/20/5/055102
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by the National Natural Science Foundation of China (Grant No. 20634030), Key Natural Science Fund of Tianjin (Grant No. 07JCZDJC00700) and State Key Lab of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences Science Funds
Rights and permissions
About this article
Cite this article
Zhang, C., Wang, W., Wang, C. et al. Cytotoxicity of liver targeted drug-loaded alginate nanoparticles. Sci. China Ser. B-Chem. 52, 1382–1387 (2009). https://doi.org/10.1007/s11426-009-0178-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11426-009-0178-9