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In-vitro elution of cisplatin and fluorouracil from bi-layered biodegradable beads

  • Liu, Kuo-Sheng (Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Linkou, College of Medicine, Chang Gung University) ;
  • Pan, Ko-Ang (Department of Mechanical Engineering, Chang Gung University) ;
  • Liu, Shih-Jung (Department of Mechanical Engineering, Chang Gung University)
  • Received : 2015.01.28
  • Accepted : 2015.05.26
  • Published : 2015.06.25

Abstract

This study developed biodegradable bi-layered drug-eluting beads and investigated the in-vitro release of fluorouracil and cisplatin from the beads. To manufacture the drug-eluting beads, poly[(d,l)-lactide-co-glycolide] (PLGA) with lactide:glycolide ratios of 50:50 and 75:25 were mixed with fluorouracil or cisplatin. The mixture was compressed and sintered at $55^{\circ}C$ to form bi-layered beads. An elution method was employed to characterize the release characteristic of the pharmaceuticals over a 30-day period at $37^{\circ}C$. The influence of polymer type (i.e., 50:50 or 75:25 PLGA) and layer layout on the release characteristics was investigated. The experiment suggested that biodegradable beads released high concentrations of fluorouracil and cisplatin for more than 30 days. The 75:25 PLGA released the pharmaceuticals at a slower rate than the 50:50 PLGA. In addition, the bi-layered structure reduced the release rate of drugs from the core layer of the beads. By adopting the compression sintering technique, we will be able to manufacture biodegradable beads for long-term drug delivery of various anti-cancer pharmaceuticals.

Keywords

References

  1. Alanazi1, F.K., Alsarra, I.A., Haq, N., Radwan, A.A. and Shakeel, F. (2014), "Potential of lipid nanoemulsion for drug delivery of cholesteryl-hexahydrophthaloyl-5-fluorouracil", J. Drug Deliv. Sci. Technol., 24(5), 459-463. https://doi.org/10.1016/S1773-2247(14)50088-3
  2. Anand, D., Dowell, J.A., Sancho, A.R. and Wolf, W. (2000), "Noninvasive measurements for studying the tumoral pharmacokinetics of platinum anticancer drugs in solid tumors", Adv. Drug Deliv. Rev., 41(1), 111-126. https://doi.org/10.1016/S0169-409X(99)00059-9
  3. Bai, M.Y. and Liu, S.Z. (2014), "Simple and general method for preparing antibody-PEG-PLGA sub-micron particles using electrospray technique: An in vitro study of targeted delivery of cisplatin to ovarian cancer cells", Colloid. Surf. B: Biointerfaces, 117, 346-353. https://doi.org/10.1016/j.colsurfb.2014.02.051
  4. Blanco, E., Gao, J. and Weinberg, B.D. (2008), "Polymer implants for intratumoral drug delivery and cancer therapy", J. Pharma Sci., 97(5), 1681-1702. https://doi.org/10.1002/jps.21038
  5. Chan, E.C., Chen, J.K., Chi, P.S., Lin, S.S., Liu, S.J. and Ueng, S.W.N. (2007), "Novel solvent-free fabrication of biodegradable poly-lactic-glycolic Acid (PLGA) capsules for antibiotics and rhBMP-2 delivery", Int. J. Pharma., 330(1-2), 45-53. https://doi.org/10.1016/j.ijpharm.2006.08.036
  6. Chung, Y.I., Kim, J.C., Kim, K., Kim, Y.H., Kwon I.C., Lee, S.Y. and Tae, G. (2010), "The effect of surface functionalization of PLGA nanoparticles by heparin-or chitosan-conjugated Pluronic on tumor targeting", J. Control. Release, 143(3), 374-382. https://doi.org/10.1016/j.jconrel.2010.01.017
  7. Conchita, Tros de Ilarduya, Daniel, M., Inigo, N., Maria, J.G. and Sara, Z. (2010), "Pharmacodynamics of cisplatin-loaded PLGA nanoparticles administered to tumor-bearing mice", Eur. J. Pharmaceutics Biopharmaceutics, 74(2), 265-274. https://doi.org/10.1016/j.ejpb.2009.10.005
  8. Crawford, J., Dale, D.C. and Lyman, G.H. (2004), "Chemotherapy-induced neutropenia: Risks, consequences, and new directions for its management", Cancer, 100(2), 228-237. https://doi.org/10.1002/cncr.11882
  9. Di, W., Duan, Y., Gu, L., Liu, P., Qiu, L., Sun, Y., Wang, Y. and Zhu, M. (2013), "Toxicity and therapy of cisplatin-loaded EGF modified mPEG-PLGA-PLL nanoparticles for SKOV3 cancer in mice", Biomater., 34(16), 4068-4077. https://doi.org/10.1016/j.biomaterials.2012.12.033
  10. Einhorn, L.H. (1990), "Treatment of testicular cancer: a new and improved model", J. Clin. Oncol., 8(11), 1777-1781. https://doi.org/10.1200/JCO.1990.8.11.1777
  11. El-Kareh, A.W. and Secomb, T.W. (2000), "A mathematical model for comparison of bolus injection, continuous infusion, and liposomal delivery of doxorubicin to tumor cells", Neoplasia, 2(4), 325-338. https://doi.org/10.1038/sj.neo.7900096
  12. Gillams, A.R. (2005), "Image guided tumour ablation", Cancer Imag., 5(1), 103-109. https://doi.org/10.1102/1470-7330.2005.0015
  13. Harkin, D.P., Johnston, P.G. and Longley, D.B. (2003), "5-fluorouracil: mechanisms of action and clinical strategies", Natl. Rev. Cancer, 3(5), 330-338. https://doi.org/10.1038/nrc1074
  14. Kau, Y.C., Liu, K.S., Liu, S.J., Peng, Y.J. and Wen, C.W. (2010), "Solvent-free biodegradable scleral plugs providing sustained release of vancomycin, amikacin and dexamethasone-An in vivo study", J. Biomed. Mater. Res. Part A, 94(2), 426-432.
  15. Middleton, J.C. and Tipton, A.J. (2000), "Synthetic biodegradable polymers as orthopedic devices", Biomater., 21(23), 2335-2346. https://doi.org/10.1016/S0142-9612(00)00101-0
  16. Peter, G.J. and Van Groeningen, C.J. (1991), "Clinical relevance of biochemical modulation of 5-fluorouracil", Ann. Oncol., 2(7), 469-480. https://doi.org/10.1093/oxfordjournals.annonc.a057994
  17. Sanjeeb, K.S. and Sarbari, A. (2011), "PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect", Adv. Drug Deliv. Rev., 63(3), 170-183. https://doi.org/10.1016/j.addr.2010.10.008
  18. Wallace, K.B. (2003), "Doxorubicin-induced cardiac mitochondrionopathy", Pharmacol Toxicol, 93(3), 105-115. https://doi.org/10.1034/j.1600-0773.2003.930301.x