Abstract
Herein, solid lipid nanoparticles (SLN) were proposed as a new drug delivery system for adefovir dipivoxil (ADV). The octadecylamine-fluorescein isothiocynate (ODA-FITC) was synthesized and used as a fluorescence maker to be incorporated into SLN to investigate the time-dependent cellular uptake of SLN by HepG2.2.15. The SLN of monostearin with ODA-FITC or ADV were prepared by solvent diffusion method in an aqueous system. About 15 wt% drug entrapment efficiency (EE) and 3 wt% drug loading (DL) could be reached in SLN loading ADV. Comparing with free ADV, the inhibitory effects of ADV loaded in SLN on hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA levels in vitro were significantly enhanced.
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Dai, C.Y., Chuang, W.L., Hsieh, M.Y., Lee, L.P., Huang, J.F., Hou, N.J., Lin, Z.Y., Chen, S.C., Hsieh, M.Y., Wang, L.Y., et al., 2007. Adefovir dipivoxil treatment of lamivudine-resistant chronic hepatitis B. Antiviral. Res., 75(2):146–151. [doi:10.1016/j.antiviral.2007.02.003]
Hadziyannis, S.J., Tassopoulos, N.C., Jenny Heathcote, E., Chang, T.T., Kitis, G., Rizzetto, M., Marcellin, P., Lim, S.G., Goodman, Z., Wulfsohn, M.S., et al., 2003. Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B. N. Engl. J. Med., 348(9):800–807. [doi:10.1056/NEJMoa021812]
Hu, F.Q., Jiang, S.P., Du, Y.Z., Yuan, H., Ye, Y.Q., Zeng, S., 2005. Preparation and characterization of stearic acid nanostructured lipid carriers by solvent diffusion method in an aqueous system. Colloid and Surfaces B-Biointerfaces, 45(3–4):167–173. [doi:10.1016/j.colsurfb.2005.08.005]
Iyer, R.P., Padmanabhan, S., Zhang, G.R., Morrey, J.D., Korba, B.E., 2005. Nucleotide analogs as novel anti-hepatitis B virus agents. Curr. Opin. Pharmacol., 5(5):520–528. [doi:10.1016/j.coph.2005.04.019]
Jiang, J.T., Xu, N., Zhang, X.Y., Wu, C.P., 2007. Lipids changes in liver cancer. J. Zhejiang Univ. Sci. B, 8(6):398–409. [doi:10.1631/jzus.2007.B0398]
Lai, C.L., Ratziu, V., Yuen, M.F., Poynard, T., 2003. Viral hepatitis B. Lancet, 362(9401):2089–2094. [doi:10.1016/S0140-6736(03)15108-2]
Marcellin, P., Chang, T.T., Lim, S.G., Tong, M.J., Sievert, W., Shiffman, M.L., Jeffers, L., Goodman, Z., Wulfsohn, M.S., Xiong, S., et al., 2003. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N. Engl. J. Med., 348(9):808–816. [doi:10.1056/NEJMoa020681]
Marengo, E., Cavalli, R., Caputo, O., Rodriguez, L., Gasco, M., 2000. Scale-up of the preparation process of solid lipid nanospheres. Int. J. Pharm., 205(1–2):3–13. [doi:10.1016/S0378-5173(00)00471-3]
Mehnert, W., Mäder, K., 2001. Solid lipid nanoparticles: production, characterization and applications. Adv. Drug Deliv. Rev., 47(2–3):165–196. [doi:10.1016/S0169-409X(01)00105-3]
Müller, R., Mäder, K., Gohla, S., 2000. Solid lipid nanoparticles (SLN) for controlled drug delivery—a review of the state of the art. Eur. J. Pharm. Biopharm., 50(1):161–177. [doi:10.1016/S0939-6411(00)00087-4]
Perrillo, R., Schiff, E., Yoshida, E., Statler, A., Hirsch, K., Wright, T., Gutfreund, K., Lamy, P., Murray, A., 2000. Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants. Hepatology, 32(1):129–134. [doi:10.1053/jhep.2000.8626]
Perrillo, R., Hann, H.W., Mutimer, D., Willems, B., Leung, N., Lee, W.M., Moorat, A., Gardner, S., Woessner, M., Bourne, E., Brosgart, C.L., Schiff, E., 2004. Adefovir dipivoxil added to ongoing lamivudine in chronic hepatitis B with YMDD mutant hepatitis B virus. Gastroenterology, 126(1):81–90. [doi:10.1053/j.gastro.2003.10.050]
Raney, A.K., Hamatake, R.K., Hong, Z., 2003. Agents in clinical development for the treatment of chronic hepatitis B. Expert Opin. Investig. Drugs, 12(8):1281–1295. [doi:10.1517/13543784.12.8.1281]
Westland, C.E., Yang, H., Delaney IV, W.E., Wulfsohn, M., Lama, N., Gibbs, C.S., Miller, M.D., Fry, J., Brosgart, C.L., Schiff, E.R., Xiong, S., 2005. Activity of adefovir dipivoxil against all patterns of lamivudine-resistant hepatitis B viruses in patients. J. Viral Hepat., 12(1):67–73. [doi:10.1111/j.1365-2893.2005.00578.x]
Yuan, H., Chen, J., Du, Y.Z., Hu, F.Q., Zeng, S., 2007. Studies on oral absorption of stearic acid SLN by a novel fluorometric method. Colloid and Surfaces B-Biointerfaces, 58(2):157–164. [doi:10.1016/j.colsurfb.2007.03.002]
Yuan, H., Miao, J., Du, Y.Z., You, J., Hu, F.Q., Zeng, S., 2008. Cellular uptake of solid lipid nanoparticles and cytotoxicity of encapsulated paclitaxel in A549 cancer cells. Int. J. Pharm., 348(1–2):137–145. [doi:10.1016/j.ijpharm.2007.07.012]
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Xing-guo, Z., Jing, M., Min-wei, L. et al. Solid lipid nanoparticles loading adefovir dipivoxil for antiviral therapy. J. Zhejiang Univ. Sci. B 9, 506–510 (2008). https://doi.org/10.1631/jzus.B0820047
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DOI: https://doi.org/10.1631/jzus.B0820047
Key words
- Adefovir dipivoxil (ADV)
- Solid lipid nanoparticles (SLN)
- Octadecylamine-fluorescein isothiocynate (ODA-FITC)
- Hepatitis B virus (HBV)