DOI QR코드

DOI QR Code

Physiochemical Properties of Binary Pluronic Systems for Reversal of Multi-drug Resistant (MDR) Cancers

  • Yun, Jung-Min (College of Pharmacy, Chung-Ang University) ;
  • Park, Ga-Young (College of Pharmacy, Chung-Ang University) ;
  • Kim, Ha-Hyung (College of Pharmacy, Chung-Ang University) ;
  • Lee, Jae-Hwi (College of Pharmacy, Chung-Ang University) ;
  • Lee, Eun-Seong (Division of Biotechnology, The Catholic University of Korea) ;
  • Youn, Yu-Seok (College of Pharmacy, Pusan National University) ;
  • Lee, Beom-Jin (Bioavailability Control Laboratory, College of Pharmacy, Kangwon National University) ;
  • Oh, Young-Taik (Department of Diagnostic Radiology, Research Institute of Radiological Science, College of Medicine, Yonsei University) ;
  • Oh, Kyung-Taek (College of Pharmacy, Chung-Ang University)
  • Received : 2010.07.21
  • Accepted : 2010.08.13
  • Published : 2010.08.20

Abstract

Pluronic as pharmaceutical excipients are listed in the US and British Pharmacopoeia. In particular, Pluronics exist as different compositions and display abundant phases as self-assembling into polymeric micelles with various morphologies depending on the aqueous solvent quality, the composition of structure, and hydrophilic-lipophilic balance (HLB). Pluronics were also known as a P-gp modulator, which was exploited as a reversal molecule of multi-drug resistant (MDR) cancers. We selected a lamella forming Pluronic L92 which has high hydrophobicity and relatively long PEO block among L series of Pluronics. The dispersion of L92 showed great size particles and low stability. To increase the stability and to decrease the particle size, secondary Pluronics (F68, F88, F98, F127, P85, P105, and P123) with relatively long PEO chain were added into 0.1 wt% Pluronic L92 dispersion. The stability of binary systems was increased due to incorporated long PEO chain. Their particle sizes slightly decreased to over 200~400 nm and their solubilization capacity of binary systems didn't change except Pluronic L92/P123 mixtures. The L92/P123 systems showed ca. 100 nm sizes and lowest turbidity among the all systems. The solubilization capacity of 0.1 wt% L92/0.1 wt% P123 was slightly increased compared to 0.1 wt% L92 mono system and other binary systems. These nano-sized binary systems may have potential as alternative drug delivery systems with simple preparation method and overcome the drawbacks of mono systems such as low stability and loading capacity.

Keywords

References

  1. Alakhov, V., Klinski, E., Lemieux, P., Pietrzynski, G., Kabanov, A., 2001. Block copolymeric biotransport carriers as versatile vehicles for drug delivery. Expert Opinion on Biological Therapy. 1, 583-602. https://doi.org/10.1517/14712598.1.4.583
  2. Alakhov, V., Klinski, E., Li, S., Pietrzynski, G., Venne, A., Batrakova, E., Bronitch, T., Kabanov, A.V., 1999. Block copolymer-based formulation of doxorubicin. From cell screen to clinical trials. Colloids Surf., B: Biointerfaces. 16, 113-134. https://doi.org/10.1016/S0927-7765(99)00064-8
  3. Allen, C., Maysinger, D., Eisenberg, A., 1999. Nano-engineering block copolymer aggregates for drug delivery. Colloids and Surfaces B: Biointerfaces. 16, 3-27. https://doi.org/10.1016/S0927-7765(99)00058-2
  4. Allison, A.C., Byars, N.E., 1986. An adjuvant formulation that selectively elicits the formation of antibodies of protective isotypes and of cell-mediated immunity. J. Immunol. Methods. 95, 157-168. https://doi.org/10.1016/0022-1759(86)90402-3
  5. Allison, A.C., Byars, N.E., 1990. Adjuvant formulations and their mode of action. Semin. Immunol. 2, 369-374.
  6. BASF Pluronic and Tetronic Surfactants. Wyandotte, BASF Corp.
  7. Batrakova, E., Lee, S., Li, S., Venne, A., Alakhov, V., Kabanov, A., 1999a. Fundamental relationships between the composition of pluronic block copolymers and their hypersensitization effect in MDR cancer cells. Pharm Res. 16, 1373-9. https://doi.org/10.1023/A:1018942823676
  8. Batrakova, E.V., Lee, S., Li, S., Venne, A., Alakhov, V., Kabanov, A., 1999b. Fundamental relationships between the composition of pluronic block copolymers and their hypersensitization effect in MDR cancer cells. Pharm. Res. 16, 1373-1379. https://doi.org/10.1023/A:1018942823676
  9. Batrakova, E.V., Miller, D.W., Li, S., Alakhov, V.Y., Kabanov, A.V., Elmquist, W.F., 2001. Pluronic P85 enhances the delivery of digoxin to the brain: in vitro and in vivo studies. J. Pharmacol. Exp. Ther. 296, 551-557.
  10. Chaibundit, C., Ricardo, N.M.P.S., Costa, F.d.M.L.L., Yeates, S.G., Booth, C., 2007. Micellization and Gelation of Mixed Copolymers P123 and F127 in Aqueous Solution. Langmuir. 23, 9229-9236. https://doi.org/10.1021/la701157j
  11. Gaisford, S., Beezer, A.E., Mitchell, J.C., 1997. Diode-Array UV Spectrometric Evidence for Cooperative Interactions in Binary Mixtures of Pluronics F77, F87, and F127. Langmuir. 13, 2606-2607. https://doi.org/10.1021/la962033r
  12. Kabanov, A.V., Alakhov, V.Y., 2002. Pluronic block copolymers in drug delivery: from micellar nanocontainers to biological response modifiers. Crit. Rev. Ther. Drug Carrier Syst. 19, 1-72. https://doi.org/10.1615/CritRevTherDrugCarrierSyst.v19.i1.10
  13. Kabanov, A.V., Batrakova, E.V., Alakhov, V.Y., 2002. Pluronic block copolymers for overcoming drug resistance in cancer. Adv Drug Deliv Rev. 54, 759-79. https://doi.org/10.1016/S0169-409X(02)00047-9
  14. Kataoka, K., Kabanov, A., Eds. (1999). Special Issue: Polymeric Micelles in Biology and Pharmaceutics, Colloids and Surfaces, B: Biointerfaces. Amsterdam, Lausanne, New York, Oxford, Shannon, Tokyo, Elsevier.
  15. Kozlov, M.Y., Melik-Nubarov, N.S., Batrakova, E.V., Kabanov, A.V., 2000. Relationship between pluronic block copolymer structure, critical micellization concentration and partitioning coefficients of low molecular mass solutes. Macromolecules. 33, 3305-3313. https://doi.org/10.1021/ma991634x
  16. Kwon, G.S., Kataoka, K., 1995. Block copolymer micelles as long-circulating drug vehicles. Advanced Drug Delivery Reviews. 16, 295-309. https://doi.org/10.1016/0169-409X(95)00031-2
  17. Langer, R., 1998. Drug delivery and targeting. Nature. 392, 5-10.
  18. Lee, E.S., Na, K., Bae, Y.H., 2005. Super pH-sensitive multi-functional polymeric micelle. Nano Lett. 5, 325-9. https://doi.org/10.1021/nl0479987
  19. Lee, E.S., Oh, Y.T., Youn, Y.S., Nam, M., Park, B., Yun, J., Kim, J.H., Song, H.-T., Oh, K.T., 2010. Binary mixing of micelles using Pluronics for a nanosized drug delivery system Colloids and Surfaces B: Biointerfaces. in submission.
  20. Lee, E.S., Shin, H.J., Na, K., Bae, Y.H., 2003. Poly(L-histidine)-PEG block copolymer micelles and pH-induced destabilization. J Control Release. 90, 363-74. https://doi.org/10.1016/S0168-3659(03)00205-0
  21. Nagarajan, R., 1999. Solubilization of hydrocarbons and resulting aggregate shape transitions in aqueous solutions of Pluronic?(PEO-PPO-PEO) block copolymers. Colloids and Surfaces B: Biointerfaces. 16, 55-72. https://doi.org/10.1016/S0927-7765(99)00061-2
  22. Oh, K.T., Bronich, T.K., Kabanov, A.V., 2004. Micellar formulations for drug delivery based on mixtures of hydrophobic and hydrophilic Pluronic block copolymers. J Control Release. 94, 411-22. https://doi.org/10.1016/j.jconrel.2003.10.018
  23. Oh, K.T., Lee, E.S., Kim, D., Bae, Y.H., 2008. L-histidine-based pH-sensitive anticancer drug carrier micelle: reconstitution and brief evaluation of its systemic toxicity. Int J Pharm. 358, 177-83. https://doi.org/10.1016/j.ijpharm.2008.03.003
  24. Torchilin, V.P., 1999. Polymeric micelles in diagnostic imaging. Colloids and Surfaces B: Biointerfaces. 16, 305-319. https://doi.org/10.1016/S0927-7765(99)00081-8
  25. Wang, Y., Yu, L., Han, L., Sha, X., Fang, X., 2007. Difunctional Pluronic copolymer micelles for paclitaxel delivery: Synergistic effect of folate-mediated targeting and Pluronic-mediated overcoming multidrug resistance in tumor cell lines. International Journal of Pharmaceutics. 337, 63-73. https://doi.org/10.1016/j.ijpharm.2006.12.033