DOI QR코드

DOI QR Code

Effect of Tripolyphosphate (TPP) on the Controlled Release of Cyclosporin A from Chitosan-coated Lipid Microparticles

  • Cheon, Ji-Woong (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Shim, Chang-Koo (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Chung, Suk-Jae (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Kim, Dae-Duk (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
  • Published : 2009.02.20

Abstract

Soybean phosphatidylcholine microparticles loaded with cyclosporin A (CsA) were prepared by the modified emulsion solvent diffusion and ionic gelation method, in which chitosan on the surface of the microparticles was crosslinked with various concentrations of tripolyphosphate (TPP). The morphology of the particles was characterized by scanning electron microscopy (SEM). The change of particle size and zeta-potential by chitosan on the surface of the lipid microparticles were systematically observed. The encapsulation efficiency and loading capacity of CsA in the particles were determined by high performance liquid chromatography (HPLC). In vitro release kinetics was studied using the dialysis method. In the results, the mean particle size and the zeta-potential of lipid microparticles increased when the attached chitosan was cross-linked (from 2.5 to 6.2 ${\mu}m$ and from -37.0 to +93.0 mV, respectively). The cyclosporin A-loaded lipid microparticles appeared discrete and spherical particles with smooth surfaces. The encapsulation efficiency of CsA was between 79% and 90% while the loading capacity was between 41% and 56%. In vitro release study showed that the crosslinkage of chitosan by TPP significantly delayed the release of CsA from the particles in a concentration-dependent manner. Thus, the release of CsA from the lipid microparticles could be controlled by tripolyphosphate used as a cross-linking agent.

Keywords

References

  1. S. Venkataram, W.M. Awni, K. Jordan and Y.E. Rahman, Pharmacokinetics of two alternative dosage forms for cyclosporine: liposomes and intralipid, J. Pharm. Sci., 79, 216-219 (1990). https://doi.org/10.1002/jps.2600790307
  2. C.K. KIM, S.A. Ryuu, K.M. Park, S.J. Lim and S.J. Hwang, Preparation and physicochemical characterization of phase inverted water/oil microemulsion containing cyclosporin A, Int. J. Pharm., 147, 131-134 (1997). https://doi.org/10.1016/S0378-5173(96)04791-6
  3. E. Ugazio, R. Cavalli and M.R. Gasco, Incorporation of cyclosporin A in solid lipid nanoparticles (SLN), Int. J. Pharm., 241, 341-344 (2002). https://doi.org/10.1016/S0378-5173(02)00268-5
  4. M.H. El-Shabouri, Positivery charged nanoparticles for improving the oral bioavailability of cyclosporine-A, Int. J. Pharm., 249, 101-108 (2002). https://doi.org/10.1016/S0378-5173(02)00461-1
  5. A.M. De Campos, A. Sánchez and M. J. Alonso, Chitosan nanoparticles: a new vehicle for the improvement of the delivery of drugs to the ocular surface. Application to cyclosporin A, Int. J. Pharm, 224, 159-168 (2001). https://doi.org/10.1016/S0378-5173(01)00760-8
  6. T. Niwa, H. Takeuchi, T. Hino, N. Kunou and Y. Kawashima, In vitro drug release behavior of D,L-lactide/glycolide copol-ymer (PLGA) nanospheres with nafarelin acetate prepared by a novel spontaneous emulsification solvent diffusion method, J. Pharm. Sci., 83, 727-732 (1994). https://doi.org/10.1002/jps.2600830527
  7. K. A. Janes, M.P. Fresneau, A. Marazuela, A. Fabra and M.J. Alonso, Chitosan nanoparticles as delivery systems for doxorubicin, J. Control. Rel., 73, 255-267 (2001). https://doi.org/10.1016/S0168-3659(01)00294-2
  8. A. Sanchez, J. V. Jato and M.J. Alonso, Development of biodegradable microspheres and nanospheres for the controlled release of cyclosporin A, Int.J.Pharm., 15, 263-273 (1993). https://doi.org/10.1016/0378-5173(93)90369-Q
  9. J. A. Ko, H. J. Park, S. J. Hwang, J. B. Park and J. S. Lee, Preparation and characterization of chitosan microparticles intended for controlled drug delivery, Int.J.Pharm., 249, 165-174 (2002). https://doi.org/10.1016/S0378-5173(02)00487-8
  10. A. K. Anal, W.F. Stevens and C.R. Lopez, Ionotropic crosslinked chitosan microspheres for controlled release of ampicillin, Int.J.Pharm., 312, 166-173 (2006). https://doi.org/10.1016/j.ijpharm.2006.01.043