Effects of Pluronic Block Copolymers on Drug Absorption in Caco-2 Cell Monolayers


Purpose. The present work characterizes the effects of Pluronic copolymers on the transport of a P-gp-dependent probe, rhodamine 123 (R123) in Caco-2 cell monolayers.

Methods. The accumulation and efflux studies were performed on the confluent Caco-2 monolayers using fluorescent probes with and without Pluronic copolymers.

Results. At concentrations below the critical micelle concentration single chains ("unimers”) of Pluronic P85 enhanced the accumulation and inhibited the efflux of R123 in Caco-2 monolayers. The transport of the P-gp-independent probe, rhodamine 110 was not altered under these conditions. In contrast the micelles increased R123 accumulation to a much lower extent when compared to the unimers and enhanced R123 efflux in Caco-2 monolayers.

Conclusions. Pluronic P85 unimers increase accumulation of a P-gp-dependent drug in Caco-2 monolayers through inhibition of the P-gp efflux system. The mechanism of the micelle effect is not known, however, it is very similar to the micelle effects in BBMEC. This has been previously shown to involve vesicular transport of the micelle-incorporated drug. The study suggests that Pluronic copolymers can be useful in increasing oral absorption of select drugs.

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  1. 1.

    S. Y. Lin and Y. Kawashima. Pluronic surfactants affecting diazepam solubility, compatibility, and adsorbtion from i.v. admixture solutions. J. Parenter. Sci. Technol. 41:83-87 (1987).

    Google Scholar 

  2. 2.

    A. V. Kabanov, V. P. Chekhonin, V. Yu. Alakhov, E. V. Batrakova, A. S. Lebedev, N. S. Melik-Nubarov, S. A. Arzhakov, A. V. Levashov, G. V. Morozov, E. S. Severin, and V. A. Kabanov. The neuroleptic activity of haloperidol increases after its solubilization in surfactant micelles. Micelles as microcontainers for drug targeting. FEBS Lett 258:343-345 (1989).

    Google Scholar 

  3. 3.

    A. Rolland, J. O'Mullane, P. Goddard, L. Brookman, and K. Petrak. New macromolecular carriers for drugs. 1. Preparation and characterization of poly(oxyethylene-b-isoprene-b-oxyethylene) block copolymer aggregates. J. Appl. Polym. Sci. 44:1195-1203 (1992).

    Google Scholar 

  4. 4.

    G. S. Kwon, M. Naito, M. Yokoyama, T. Okano, Y. Sakurai, and K. Kataoka. Physical entrapment of adriamycin in AB block copolymer micelles. Pharm. Res. 12:192-195 (1995).

    Google Scholar 

  5. 5.

    S. A. Hagan, A. G. A. Coombes, M. C. Garnett, S. E. Dunn, M. C. Davies, L. Illum, S. S. Davis, S. E. Harding, S. Purkiss, and P. R. Gellert. Polylactide-poly(ethylene glycol) copolymers as drug delivery systems. 1. Characterization of water dispersible micelle-forming systems. Langmuir 12:2153-2161 (1996).

    Google Scholar 

  6. 6.

    X. Zhang, J. K. Jackson, and H. M. Burt. Development of amphiphilic block copolymers as micellar carriers of taxol. Int. J. Pharm. 132:195-206 (1996).

    Google Scholar 

  7. 7.

    A. V. Kabanov, E. V. Batrakova, N. S. Melik-Nubarov, N. A. Fedoseev, T. Yu. Dorodnich, V. Yu. Alakhov, V. P. Chekhonin, I. R. Nazarova, and V. A. Kabanov. A new class of drug carriers: micelles of poly(oxyethylene)-poly(oxypropylene) block copolymers as microcontainers for drug targeting from blood in brain. J. Contr. Release 22:141-158 (1992).

    Google Scholar 

  8. 8.

    D. W. Miller, E. V. Batrakova, T. O. Waltner, V. Yu. Alakhov, and A. V. Kabanov. Interactions of Pluronic block copolymers with brain microvessel endothelial cells: evidence for multiple absorption pathways. Bioconjugate Chem. 8:649-657 (1997).

    Google Scholar 

  9. 9.

    K. I. Hosoya, K. J. Kim, and V. H. Lee. Age-dependent expression of P-glycoprotein gp170 in Caco-2 cell monolayers. Pharm. Res. 13:885-890 (1996).

    Google Scholar 

  10. 10.

    G. Wilson. Cell culture techniques for the study of drug transport. Eur. J. Drug Metab. Pharmacokinet. 15:159-163 (1990).

    Google Scholar 

  11. 11.

    J. Fogh, J. M. Fogh, and T. J. Orfeo. One hundred and twenty seven cultured human cell lines producing tumors in nude mice. J. Natl. Cancer Inst. 59:221-226 (1977).

    Google Scholar 

  12. 12.

    P. Artursson. Epithelial transport of drugs in cell culture. I: A model for studying the passive diffusion of drugs over intestinal absorptive (Caco-2) cells. J. Pharm. Sci. 79:476-482 (1990).

    Google Scholar 

  13. 13.

    M. Fontaine, W. F. Elmquist, and D. W. Miller. Use of rhodamine 123 to examine the functional activity of P-glycoprotein in primary cultured brain microvessel endothelial cell monolayers. Life Sci. 59:1521-1531, 1996.

    Google Scholar 

  14. 14.

    T. J. Lampidis, C. Castello, A. Del Giglio, B. C. Pressman, P. Viallet, K. W. Trevorrow, G. K. Valet, H. Tapiero, and N. Savaraj. Relevance of the chemical charge of rhodamine dyes to multiple drug resistance. Biochem. Pharmacol. 38:4267-4271 (1989).

    Google Scholar 

  15. 15.

    A. V. Kabanov, I. R. Nazarova, I. V. Astafieva, E. V. Batrakova, V. Yu. Alakhov, A. A. Yaroslavov, and V. A. Kabanov. Micelle formation and solubilization of fluorescent probes in poly(oxyethylene-b-oxypropylene-b-oxyethylene) solutions. Macromolecules 28:2303-2314 (1995).

    Google Scholar 

  16. 16.

    M. M. Nerurkar, P. S. Burton, and R. T. Borchardt. The use of surfactants to enhance the permeability of peptides through Caco-2 cells by inhibition of an apically polarized efflux system. Pharm. Res. 13:528-534 (1996).

    Google Scholar 

  17. 17.

    P. K. Dudeja, K. M. Anderson, J. S. Harris, L. Buckingham and J. S. Coon. Reversal of multidrug resistance phenotype by surfactants: relationship to membrane lipid fluidity. Arch. Biochem. Biophys. 319:309-315 (1995).

    Google Scholar 

  18. 18.

    V. Yu. Alakhov, E. Yu. Moskaleva, E. V. Batrakova and A. V. Kabanov. Hypersensitization of multidrug resistant human ovarian carcinoma cells by Pluronic P85 block copolymer. Bioconjugate Chem. 7:209-216 (1996).

    Google Scholar 

  19. 19.

    A. Venne, S. Li, R. Mandeville, A. V. Kabanov and V. Yu. Alakhov. Hypersensitizing effect of Pluronic L61 on cytotoxic activity, transport, and subcellular distribution of doxorubicin in multiple drug-resistant cells. Cancer Research 56:3626-3629 (1996).

    Google Scholar 

  20. 20.

    M. M. Nerurkar, N. F. H. Ho, P. S. Burton, T. J. Vidmar and R. T. Borchardt. Mechanistic roles of neutral surfactants on concurrent polarized and passive membrane transport of a model peptide in Caco-2 cells. J. Pharm. Sci. 7:813-821 (1997).

    Google Scholar 

  21. 21.

    P. Alexandridis, V. Athanassiou, S. Fukuda, and T. A. Hatton. Surface activity of poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) copolymers. Langmuir 10:2604-2612 (1994).

    Google Scholar 

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Batrakova, E.V., Han, HY., Alakhov, V.Y. et al. Effects of Pluronic Block Copolymers on Drug Absorption in Caco-2 Cell Monolayers. Pharm Res 15, 850–855 (1998). https://doi.org/10.1023/A:1011964213024

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  • block copolymer
  • intestinal delivery
  • drug
  • micelles