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Pharmacokinetics and biodegradation of chitosan in rats

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Abstract

Chitosan, an excellent biomedical material, has received a widespread in vivo application. In contrast, its metabolism and distribution once being implanted were less documented. In this study, the pharmacokinetics and biodegradation of fluorescein isothiocyanate (FITC) labeled and muscle implantation administrated chitosan in rats were investigated with fluorescence spectrophotometry, histological assay and gel chromatography. After implantation, chitosan was degraded gradually during its distribution to diverse organs. Among the tested organs, liver and kidney were found to be the first two highest in chitosan content, which was followed by heart, brain and spleen. Urinary excretion was believed to be the major pathway of chitosan elimination, yet 80% of chitosan administered to rats was not trackable in their urine. This indicated that the majority of chitosan was degraded in tissues. In average, the molecular weight of the degradation products of chitosan in diverse organs and urine was found to be <65 kDa. This further confirmed the in vivo degradation of chitosan. Our findings provided new evidences for the intensive and safe application of chitosan as a biomedical material.

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References

  • Acosta, N., Jimenez, C., Borau, V., and Heras, A., 1993. Extraction and characterization of chitin from crustaceans. Biomass Bioenergy, 5: 145–53.

    Article  Google Scholar 

  • Aicher, A., Brenner, W., Zuhayra, M., Badorff, C., Massoudi, S., Assmus, B., and Dimmeler, S., 2003. Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling. Circulation, 107 (16): 2134–2139.

    Article  Google Scholar 

  • Albanna, M. Z., Bou-Akl, T., Walters, H. L., and Matthew, H. W. T., 2012. Improving the mechanical properties of chitosanbased heart valve scaffolds using chitosan fibers. Journal of the Mechanical Behavior of Biomedical Materials, 5 (1): 171–180.

    Article  Google Scholar 

  • Artandi, S. E., Chang, S., Lee, S. L., Alson, S., Gottlieb, G. J., Chin, L., and DePinho, R. A., 2000. Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice. Nature, 406 (6796): 641–645.

    Article  Google Scholar 

  • Chang, W., Chen, C., Ji, D., Lee, S., Tsai, T., Wu, H., and Yang, J., 2011. Development of a chitosan-polyglutamate based injectable polyelectrolyte complex scaffold. Carbohydrate Polymers, 85 (2): 318–324.

    Article  Google Scholar 

  • Cheng, Y., Xu, Z., Ma, M., and Xu, T., 2008. Dendrimers as drug carriers: Applications in different routes of drug administration. Journal of Pharmaceutical Sciences, 97 (1): 123–143.

    Article  Google Scholar 

  • Di Martino, A., Sittinger, M., and Risbud, M. V., 2005. Chitosan: A versatile biopolymer for orthopaedic tissue-engineering. Biomaterials, 26 (30): 5983–5990.

    Article  Google Scholar 

  • Dong, W., Han, B., Feng, Y., Song, F., Chang, J., Jiang, H., Tang, Y., and Liu, W., 2010. Pharmacokinetics and biodegradation mechanisms of a versatile carboxymethyl erivative of chitosan in rats: In vivo and in vitro evaluation. Biomacromolecules, 11 (6): 1527–1533.

    Article  Google Scholar 

  • Gad, S. C., 2008. Safety Evaluation of Medical Devices. CRC Press, 576pp.

    Google Scholar 

  • Glinsky, G. V., Glinskii, A. B., Stephenson, A. J., Hoffman, R. M., and Gerald, W. L., 2004. Gene expression profiling predicts clinical outcome of prostate cancer. Journal of Clinical Investigation, 113 (6): 913–923.

    Article  Google Scholar 

  • Gogolewski, S., 2000. Bioresorbable polymers in trauma and bone surgery. Injury, 31 (Suppl 4): 28–32.

    Article  Google Scholar 

  • Hejazi, M., and Amiji, R., 2003. Chitosan-based gastrointestinal delivery systems. Journal of Controlled Release, 89 (2): 151–165.

    Article  Google Scholar 

  • Hoppe-Seiler, F., 1994. Chitin and chitosan. Berichte der Deutschen Chemischen Gesellschaft, 27: 3329–31.

    Article  Google Scholar 

  • Huang, R., Deng, Z., Yang, C., Yin, Y., Xie, M., Wu, G., Li, T., Li, L., Tang, Z., Kang, P., Hou, Z., Deng, D., Xiang, H., Kong, X., and Guo, Y., 2007. Dietary oligochitosan supplementation enhances immune status of broilers. Journal of the Science of Food and Agriculture, 87 (1): 153–159.

    Article  Google Scholar 

  • Huang, Y., Huang, W., Ren, X. E., Wu, Y., and Yang, F., 2013. Degradation of chitosan by hydrodynamic cavitation. Polymer Degradation and Stability, 98 (1): 37–43.

    Article  Google Scholar 

  • Ikada, Y., and Tsuji, H., 2000. Biodegradable polyesters for medical and ecological applications. Macromolecular Rapid Communications, 21 (3): 117–132.

    Article  Google Scholar 

  • Jiang, M., Zhuge, X., Yang, Y., Gu, X., and Ding, F., 2009. The promotion of peripheral nerve regeneration by chitooligosaccharides in the rat nerve crush injury model. Neuroscience Letters, 454 (3): 239–243.

    Article  Google Scholar 

  • Jikakis, J. P., (ed.), 1984. Chitin, Chitosan and Related Enzymes. Academic Press, New York, 423pp.

    Google Scholar 

  • Kean, T., and Thanou, M., 2010. Biodegradation, biodistribution and toxicity of chitosan. Advanced Drug Delivery Reviews, 62 (1): 3–11.

    Article  Google Scholar 

  • Kong, X., Han, B., Wang, H., Li, H., Xu, W., and Liu, W., 2012. New biodegradable small-diameter artificial vascular prosthesis: A feasibility study. Journal of Biomedical Materials Research Part A, 100A (6): 1494–1504.

    Article  Google Scholar 

  • Madihally, S. V., and Matthew, H. W., 1999. Porous chitosan scaffolds for tissue engineering. Biomaterials, 20 (12): 1133–1142.

    Article  Google Scholar 

  • Moon, D. G., Christ, G., Stitzel, J. D., Atala, A., and Yoo, J. J., 2008. Cyclic mechanical preconditioning improves engineered muscle contraction. Tissue Engineering Part A, 14 (4): 473–482.

    Article  Google Scholar 

  • Muzzarelli, R. A. A., 1973. Natural Chelating Polymers. Pergamon Press, New York, 83–227.

    Google Scholar 

  • Notin, L., Viton, C., David, L., Alcouffe, P., Rochas, C., and Domard, A., 2006. Morphology and mechanical properties of chitosan fibers obtained by gel-spinning: Influence of the dryjet-stretching step and ageing. Acta Biomaterialia, 2 (4): 387–402.

    Article  Google Scholar 

  • Onishi, H., and Machida, Y., 1999. Biodegradation and distribution of water-soluble chitosan in mice. Biomaterials, 20: 175–182.

    Article  Google Scholar 

  • Park, J. H., Cho, Y. W., Chung, H., Kwon, I. C., and Jeong, S. Y., 2003. Synthesis and characterization of sugar-bearing chitosan derivatives: Aqueous solubility and biodegradability. Biomacromolecules, 4 (4): 1087–1091.

    Article  Google Scholar 

  • Rinaudo, M., 2006. Chitin and chitosan: Properties and applications. Progress in Polymer Science, 31 (7): 603–632.

    Article  Google Scholar 

  • Sinha, V. R., Singla, A. K., Wadhawan, S., Kaushik, R., Kumria, R., Bansal, K., and Dhawan, S., 2004. Chitosan microspheres as a potential carrier for drugs. International Journal of Pharmaceutics, 274 (1-2): 1–33.

    Article  Google Scholar 

  • Tsaih, M. L., Tseng, L. Z., and Chen, R. H., 2004. Effects of removing small fragments with ultrafiltration treatment and ultrasonic conditions on the degradation kinetics of chitosan. Polymer Degradation and Stability, 86 (1): 25–32.

    Article  Google Scholar 

  • Varia, S. A., Schuller, S., Sloan, K. B., and Stella, V. J., 1984. Phenytoin prodrugs III: Water-soluble prodrugs for oral and/or parenteral use. Journal of Pharmaceutical Sciences, 73 (8): 1068–1073.

    Article  Google Scholar 

  • Xia, W., Liu, P., Zhang, J., and Chen, J., 2011. Biological activities of chitosan and chitooligosaccharides. Food Hydrocolloids, 25 (2): 170–179.

    Article  Google Scholar 

  • Zeng, L., Qin, C., Wang, W., Chi, W., and Li, W., 2008. Absorption and distribution of chitosan in mice after oral administration. Carbohydrate Polymers, 71 (3): 435–440.

    Article  Google Scholar 

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Correspondence to Wanshun Liu.

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Li, H., Jiang, Z., Han, B. et al. Pharmacokinetics and biodegradation of chitosan in rats. J. Ocean Univ. China 14, 897–904 (2015). https://doi.org/10.1007/s11802-015-2573-5

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  • DOI: https://doi.org/10.1007/s11802-015-2573-5

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