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Block Copolymer Micelles for the Encapsulation and Delivery of Amphotericin B

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Abstract

Purpose. To assess the effect of fatty acid substitution of a micelle-forming poly(ethylene oxide)-block-poly(N-hexyl stearate-L-aspartamide) (PEO-b-PHSA) on the encapsulation, hemolytic properties and antifungal activity of amphotericin B (AmB).

Methods. PEO-b-PHSA with three levels of stearic acid substitution were synthesized and used to encapsulate AmB by a solvent evaporation method. Size exclusion chromatography and UV spectroscopy were used to confirm and measure levels of encapsulated AmB. The hemolytic activity of encapsulated AmB toward human red blood cells and its minimum inhibitory concentration against Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans were obtained and compared to AmB alone.

Results. An increase in the level of stearic acid substitution on PEO-b-PHSA improved the encapsulation of AmB while reducing its hemolytic activity. PEO-b-PHSA micelles having 50% and 70% stearic acid substitution (mol fatty acid: mol reacted and unreacted hydroxyls) were completely non-hemolytic at 22 μg/ml. At 11% stearic acid substitution, AmB caused 50% hemolysis at 1 μg/ml. AmB in PEO-b-PHSA micelles was as effective as AmB alone against pathogenic fungi.

Conclusions. PEO-b-PHSA micelles with a high level of stearic acid side chain substitution can effectively solubilize AmB, reduce its hemolytic activity yet retain its potent antifungal effects.

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REFERENCES

  1. G. S. Kwon and T. Okano. Soluble self assembled block copolymers for drug delivery. Pharm. Res. 16:597–600 (1999).

    Google Scholar 

  2. C. Allen, D. Maysinger, and A. Eisenberg. Nano-engineering block copolymer aggregates for drug delivery. Colloids & Surfaces B: Biointerfaces 16:3–27 (1999).

    Google Scholar 

  3. M. Yokoyama, G. S. Kwon, T. Okano, Y. Sakurai, T. Sato, and K. Kataoka. Preparation of micelle-forming polymer-drug conjugates. Bioconju. Chem. 3:295–301 (1992).

    Google Scholar 

  4. Y. Li and G. S. Kwon. Micelle-like structures of poly(ethylene oxide)-block-poly(2-hydroxyethyl aspartamide)-methotrexate conjugates. Colloids & Surfaces B: Biointerfaces 16:217–226 (1999).

    Google Scholar 

  5. M. Yokoyama, S. Fukushima, R. Uehara, K. Okamoto, K. Kataoka, Y. Sakurai, and T. Okano. Characterization of physical entrapment and chemical conjugation of adriamycin in polymeric micelles and their design for in vivo delivery to a solid tumor. J. Control. Release 50:79–92 (1998).

    Google Scholar 

  6. M. Yokoyama, A. Satoh, Y. Sakurai, T. Okano, Y. Matsumura, T. Kakizoe, and K. Kataoka. Incorporation of water-insoluble anticancer drug into polymeric micelles and control of their particle size. J. Control. Release 55:219–229 (1998).

    Google Scholar 

  7. A. Lavasanifar, J. Samuel, and G. S. Kwon. Micelles of poly(ethylene oxide)-block-poly(hydroxy alkyl-L-aspartamide): synthetic analogues of lipoproteins for drug delivery. J. Biomed. Mater. Res. 52:831–835 (2000).

    Google Scholar 

  8. G. S. Kwon and K. Kataoka. Block copolymer micelles as long circulating drug vehicles. Adv. Drug Del. Rev. 16:295–309 (1995).

    Google Scholar 

  9. A. Lavasanifar, J. Samuel, and G. S. Kwon. The effect of alkyl core structure on micellar properties of poly(ethylene oxide)-block-poly(L-aspartamide) derivatives. Colloids & Surfaces B: Biointerfaces 22:115–126 (2001).

    Google Scholar 

  10. A. Lavasanifar, J. Samuel, and G. S. Kwon. Micelles selfassembled from poly(ethylene oxide)-block-poly([N-hexyl stearate]-L-aspartamide) by a solvent evaporation method: effect on the solubilization and hemolytic activity of amphotericin B. J. Control. Release 77:155–160 (2001).

    Google Scholar 

  11. J. Brajtburg and J. Bolard. Carrier effects on biologic activity of amphotericin B. Clin. Microbiol. Rev. 9:512–531 (1996).

    Google Scholar 

  12. J. Barwicz, R. Gareau, A. Audet, A. Morisset, J. Villiard, and I. Gruda. Inhibition of the interaction between lipoproteins and amphotericin B by some delivery systems. Biochem. Biophys. Res. Comun. 181:722–728 (1991).

    Google Scholar 

  13. I. Gruda and N. Dussault. Effect of the aggregation state of amphotericin B on its interaction with ergosterol. Biochem. Cell Biol. 66:177–183 (1988).

    Google Scholar 

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Authors and Affiliations

  1. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, T6G 2N8, Canada

    Afsaneh Lavasanifar, John Samuel & Saeed Sattari

  2. School of Pharmacy, University of Wisconsin-Madison, 777 Highland Ave., Madison, Wisconsin, 53705

    Glen S. Kwon

Authors
  1. Afsaneh Lavasanifar
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  2. John Samuel
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  3. Saeed Sattari
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  4. Glen S. Kwon
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Correspondence to Glen S. Kwon.

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Lavasanifar, A., Samuel, J., Sattari, S. et al. Block Copolymer Micelles for the Encapsulation and Delivery of Amphotericin B. Pharm Res 19, 418–422 (2002). https://doi.org/10.1023/A:1015127225021

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  • DOI: https://doi.org/10.1023/A:1015127225021

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