DOI QR코드

DOI QR Code

Preparation and Stability Evaluation of Docetaxel-Loaded Oral Liposome

  • Received : 2010.02.19
  • Accepted : 2010.03.30
  • Published : 2010.04.20

Abstract

Docetaxel-loaded liposomes were prepared by emulsion-solvent evaporation method, then coated with chitosan at room temperature and lyophilized. This system was designed in order to improve solubility and stability of docetaxel in the GI tract for oral drug delivery. The solubilizing effect of some frequently used solubilizers and/or liposome was determined. Among the results docetaxel-loaded liposomes prepared with 0.5% TPGS as a solubilizer showed 100-fold higher solubility than docetaxel. In a stability test, mean particle size of different liposome formulations was measured by a particle size analyzer in simulated gastric fluid (SGF) and in simulated intestinal fluid (SIF). The particle size of uncoated liposomes was significantly increased compared with that of chitosan-coated liposomes in SGF, however, there was no significant difference between coated and uncoated liposome in SIF. It is evident that chitosan-coated liposomes were more stable in GI conditions. The release characteristics of docetaxel-loaded liposomes were also investigated in three buffer solutions (pH 1.2, 4.0, 6.8). Docetaxel release did not occur in pH 1.2 for 4 hrs. However, in pH 4.0 and 6.8 conditions, docetaxel was gradually released over 24 hrs as a sustained release. It seems that aggregation and precipitation of particles by electrostatic interaction might protect docetaxel from being released. In Conclusion, the results from this study show that the chitosan-coated liposomes may be useful in enhancing solubility and GI stability of docetaxel.

Keywords

References

  1. P. Goyal, K. Goyal, S.G.V. Kumar, A. Singh, O.P. Katare and D.N. Mishra, Liposome drug delivery systems-Clinical applications, Acta. Pharm., 55, 1-25 (2005).
  2. Y. Chen, Y. Lu, J. Chen, J. Lai, J. Sun, F. Hu and W. Wu, Enhanced bioavailability of the poorly water-soluble drug fenofibrate by using liposomes containing a bile salt, Int. J. pharm., 379, 153-160 (2009).
  3. Y.A. Kim, H.D. Han, J.H. Hyun and B.C, Shin, Stability of Liposomal Nano-Powder with the addition of cryoprotectant, J. Kor. Chem. Soc., 49, No2 (2005).
  4. J. Guo, Q. Ping, G. Jiang, L. Huang and Y. Tong, Chitosancoated liposomes: characterization and interaction with leuprolide, Int. J. pharm., 260, 167-173 (2003). https://doi.org/10.1016/S0378-5173(03)00254-0
  5. H. Takeuchi, Y. Matsui, H. Sugihara, H. Yamamoto and Y. Kawashima, Effectiveness of submicron-sized, chitosancoated liposomes in oral administration of peptide drugs, Int. J. pharm. 303, 160-170 (2005). https://doi.org/10.1016/j.ijpharm.2005.06.028
  6. E.H. Kim, J.E. Lee, D.H. Lim, S.H. Jung, H. Seong, E.S. Park and B.C. Shin, Preparation of lipid nanoparticles containing paclitaxel and their in vitro gastrointestinal stability, J. Kor. Pharm. Sci., 38, 127-134 (2008).
  7. F.K. Engels, R.A. Mathot and J.Verweij, Alternative drug formulations of docetaxel:a review, Anti-Cancer Drugs., 18, 95-103 (2007) https://doi.org/10.1097/CAD.0b013e3280113338
  8. Y.M. Yin, F.D. Cui, C.F. Mu, M.K. Choi, J.S. Kim, S.J. Chung, C.K. Shim and D.D. Kim, Docetaxel microemulsion for enhanced oral bioavailability: Preparation and in vitro and in vivo evaluation, J. Control. Release, 140, 86-94 (2009). https://doi.org/10.1016/j.jconrel.2009.08.015
  9. S.S. Feng, L. Mei, P. Anitha, C.W. Gan and W. Zhou, Poly(lactide)- vitamin E derivative/montmorillonite nanoparticle formulations for the oral delivery of Docetaxel, Biomaterials., 30, 3297-3306 (2009). https://doi.org/10.1016/j.biomaterials.2009.02.045
  10. H. Takeuchi, H. Yamamoto, T. Niwa, T. Hino and Y. Kawashima, Enteral absorption of insulin in rats from mucoadhesive chitosan-coated liposomes, Pharm. Res., 13, 896-901 (1996). https://doi.org/10.1023/A:1016009313548
  11. B.J. Boyd, Y.D Dong and T. Rades, Nonlamellar liquid crystalline nanostructured particles: advances in materials and structure determination, Journal of Liposome Research, 19(1), 12-28 (2009). https://doi.org/10.1080/08982100802691983
  12. M.V.S. Varma and R. Panchagnula, Enhanced oral paclitaxel absorption with vitamin E-TPGS: Effect on solubility and permeablility in vitro, in situ and in vivo, Nonlamellar liquid crystalline nanostructured particles: advances in materials and structure determination, European Journal of pharmaceutical sciences, 25, 445-453 (2005). https://doi.org/10.1016/j.ejps.2005.04.003