Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Amphotericin B Aggregation Inhibition with Novel Nanoparticles Prepared with Poly(${\varepsilon}$-caprolactone)/Poly(N,N-dimethylamino-2-ethyl methacrylate) Diblock Copolymer

  • Shim, Yong-Ho (Laboratory of Polymeric and Composite Materials, Center for Innovation and Research in Materials and Polymers (CIRMAP), University of Mons-Hainaut) ;
  • Kim, You-Chan (Department of Food Science and Biotechnology, Sungkyunkwan University) ;
  • Lee, Hong-Joo (Gwangju Development Institute) ;
  • Bougard, Francois (Laboratory of Polymeric and Composite Materials, Center for Innovation and Research in Materials and Polymers (CIRMAP), University of Mons-Hainaut) ;
  • Dubois, Philippe (Laboratory of Polymeric and Composite Materials, Center for Innovation and Research in Materials and Polymers (CIRMAP), University of Mons-Hainaut) ;
  • Choi, Ki-Choon (Grassland and Forages Research Center, National Institute of Animal Science, Rural Development Administration) ;
  • Chung, Chung-Wook (National Research and Development Center for Hepatobiliary Disease, Pusan National University Yangsan Hospital) ;
  • Kang, Dae-Hwan (National Research and Development Center for Hepatobiliary Disease, Pusan National University Yangsan Hospital) ;
  • Jeong, Young-Il (National Research and Development Center for Hepatobiliary Disease, Pusan National University Yangsan Hospital)
  • Received : 2010.07.20
  • Accepted : 2010.10.25
  • Published : 2011.01.28
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Abstract

Diblock copolymers composed of poly(${\varepsilon}$-caprolactone) (PCL) and poly(N,N-dimethylamino-2-ethyl methacrylate) (PDMAEMA), or methoxy polyethylene glycol(PEG), were synthesized via a combination of ring-opening polymerization and atom-transfer radical polymerization in order to prepare polymeric nanoparticles as an antifungal drug carrier. Amphotericin B (AmB), a natural antibiotic, was incorporated into the polymeric nanoparticles. The physical properties of AmB-incorporated polymeric nanoparticles with PCL-b-PDMAEMA and PCL-b-PEG were studied in relation to morphology and particle size. In the aggregation state study, AmB-incorporated PCL-b- PDMAEMA nanoparticles exhibited a monomeric state pattern of free AmB, whereas AmB-incorporated PCL-b- PEG nanoparticles displayed an aggregated pattern. In in vitro hemolysis tests with human red blood cells, AmBincorporated PCL-b-PDMAEMA nanoparticles were seen to be 10 times less cytotoxic than free AmB (5 ${\mu}g$/ml). In addition, an improved antifungal activity of AmBincorporated polymeric nanoparticles was observed through antifungal activity tests using Candida albicans, whereas polymeric nanoparticles themselves were seen not to affect activity. Finally, in vitro AmB release studies were conducted, proving the potential of AmB-incorporated PCL-b-PDMAEMA nanoparticles as a new formulation candidate for AmB.

Keywords

References

  1. Adams, M. L. and G. S. Kwon. 2003. Relative aggregation state and hemolytic activity of amphotericin B encapsulated by poly(ethylene oxide)-block-poly(N-hexyl-L-aspartamide)-acyl conjugate micelles: Effects of acyl chain length. J. Control. Release 87: 23-32. https://doi.org/10.1016/S0168-3659(02)00347-4
  2. Barwicz, J., S. Christian, and I. Gruda. 1992. Effects of aggregation of amphotericin B on its toxicity to mice. Antimicrob. Agents Chemother. 36: 2310-2315. https://doi.org/10.1128/AAC.36.10.2310
  3. Berman, J. D. 1997. Human leishmaniasis: Clinical, diagnostic and chemotherapeutic developments in past 10 years. Clin. Infect. Dis. 24: 684-703. https://doi.org/10.1093/clind/24.4.684
  4. Bolard, J., P. Legrand, F. Heitz, and B. Cybulska. 1991. Onesided action of amphotericin B on cholesterol-containing membranes is determined by its self-association in the medium. Biochemistry 30: 5707-5715. https://doi.org/10.1021/bi00237a011
  5. Bougard, F., M. Jeusette, L. Mespouille, P. Dubois, and R. Lazzaroni. 2007. Synthesis and supramolecular organization of amphiphilic diblock copolymers combining poly(N,N-dimethylamino- 2-ethyl methacrylate) and poly($\varepsilon$-caprolactone). Langmuir 23: 2339-2345. https://doi.org/10.1021/la0620657
  6. Choi, K. C., J. Y. Bang, P. I. Kim, C. Kim, and C. E. Song. 2008. Amphotericin B-incorporated polymeric micelles composed of poly(D,L-lactide-co-glycolide)/dextran graft copolymer. Int. J. Pharm. 355: 224-230. https://doi.org/10.1016/j.ijpharm.2007.12.011
  7. Deray, G. 2002. Amphotericin B nephrotoxicity. J. Antimicrob. Chemother. 49: 37-41. https://doi.org/10.1093/jac/49.suppl_1.37
  8. Deshpande, M. C., M. C. Davies, M. C. Garnett, P. M. Williams, D. Armitage, L. Bailey, M. Vamvakaki, S. P. Armes, and S. Stolnik. 2004. The effect of poly(ethylene glycol) molecular architecture on cellular interaction and uptake of DNA complexes J. Control. Release 97: 143-156. https://doi.org/10.1016/j.jconrel.2004.02.019
  9. Dupont, B. 2002. Overview of the lipid formulations of amphotericin B. J. Antimicrob. Chemother. 49(Suppl S1): 31-36.
  10. Gallis, H. A., R. H. Drew, and W. W. Pickard. 1990. Amphotericin B: 30 years of clinical experience. Rev. Infect. Dis. 12: 308-329. https://doi.org/10.1093/clinids/12.2.308
  11. Gref, R., Y. Minamitake, M. T. Peracchia, V. Trubetskoy, V. Torchilin, and R. Langer. 1994. Biodegradable long-circulating polymeric nanospheres. Science 263: 1600-1603. https://doi.org/10.1126/science.8128245
  12. Groll, A. H. and T. J. Walsh. 2001. Uncommon opportunistic fungi: New nosocomial threats. Clin. Microbiol. Infect. 7(Suppl 2): 8-24.
  13. Ichinose, K., N. Tomiyama, M. Nakashima, Y. Ohya, M. Ichikawa, T. Ouchi, and T. Kanematsu. 2000. Antitumor activity of dextran derivatives immobilizing platinum complex (II). Anticancer Drugs 11: 33-38. https://doi.org/10.1097/00001813-200001000-00006
  14. Jeong, Y. I., J. B. Cheon, S. H. Kim, J. W. Nah, Y. M. Lee, Y. K. Sung, T. Akaike, and C. S. Cho. 1998. Clonazepam release from core-shell type nanoparticles in vitro. J. Control. Release 5: 169-178.
  15. Jeong, Y. I., M. K. Kang, H. S. Sun, S. S. Kang, H. W. Kim, K. S. Moon, K. J. Lee, S. H. Kim, and S. Jung. 2004. All-transretinoic acid release from core-shell type nanoparticles of poly($\varepsilon$-caprolactone)/poly(ethylene glycol) diblock copolymer. Int. J. Pharm. 273: 95-107. https://doi.org/10.1016/j.ijpharm.2003.12.012
  16. Kataoka, K., G. S. Kwon, M. Yokohama, T. Okano, and Y. Sakurai. 1993. Block copolymer micelles as vehicles for drug delivery. J. Control. Release 24: 119-132. https://doi.org/10.1016/0168-3659(93)90172-2
  17. Kwon, G. S., M. Naito, M. Yokoyama, T. Okano, Y. Sakurai, and K. Kataoka. 1995. Physical entrapment of adriamycin in AB block copolymer micelles. Pharm. Res. 12: 192-195. https://doi.org/10.1023/A:1016266523505
  18. Larabi, M., V. Yardley, P. M. Loiseau, M. Appel, P. Legrand, A. Gulik, C. Bories, S. L. Croft, and G. Barrat. 2003. Toxicity and antileishmanial activity of a new stable lipid suspension of amphotericin B. Antimicrob. Agents Chemother. 47: 3774-3779. https://doi.org/10.1128/AAC.47.12.3774-3779.2003
  19. Lavasanifar, A., J. Samuel, S. Sattari, and G. S. Kwon. 2002. Block copolymer micelles for the encapsulation and delivery of amphotericin B. Pharm. Res. 19: 418-422. https://doi.org/10.1023/A:1015127225021
  20. Legrand, P., E. Romero, J. P. Devissaguet, C. B. Eleazar, and J. Bolard. 1992. Effects of aggregation and solvent on toxicity of amphotericin B to human erythrocytes. Antimicrob. Agents Chemother. 36: 2518-2522. https://doi.org/10.1128/AAC.36.11.2518
  21. Mouton, J. W., D. T. Te Dorsthorst, J. F. Meis, and P. E. Verweij. 2009. Dose-response relationships of three amphotericin B formulations in a non-neutropenic murine model of invasive aspergillosis. Med. Mycol. 29: 1-7.
  22. Shim, Y. H., F. Bougard, R. Lazzaroni, and P. Dubois. 2008. Synthesis and aqueous solution properties of 2-(dimethylamino)ethyl methacrylate based (co)polymers: Viscometric and AFM analysis. Eur. Pol. J. 44: 3715-3723. https://doi.org/10.1016/j.eurpolymj.2008.08.016
  23. Vandermeulen, G., L. Rouxhet, A. Arien, M. E. Brewster, and V. Preat. 2006. Encapsulation of amphotericin B in poly(ethylene glycol)-block-poly($\varepsilon$-caprolactone-co-trimethylenecarbonate) polymeric micelles. Int. J. Pharm. 309: 234-240. https://doi.org/10.1016/j.ijpharm.2005.11.031
  24. Walsh, T. J., J. Hiemenz, and E. Anaissie. 1996. Recent progress and current problems in treatment of invasive fungal infections in neuropenic patients. Infect. Dis. Clin. North Am. 10: 365-400. https://doi.org/10.1016/S0891-5520(05)70303-2
  25. Yardley, V. and S. J. Croft. 1997. Activity of liposomal amphotericin B against experimental cutaneous leishmaniasis. Antimicrob. Agents Chemother. 41: 752-756.
  26. Yu, B., T. Okano, K. Kataoka, S. Sardari, and G. Kwon. 1998. In vitro dissociation of antifungal efficacy and toxicity for amphotericin B-loaded poly(ethylene oxide)-block-poly(betabenzyl-L-aspartate) micelles. J. Control. Release 56: 285-291. https://doi.org/10.1016/S0168-3659(98)00095-9
  27. Bougard, F., C. Giacomelli, L. Mespouille, R. Borsali, Ph. Dubois, and R. Lazzaroni. 2008. Influence of the macromolecular architecture on the self-assembly of amphiphilic copolymers based on poly(N,N-dimethylamino-2-ethyl methacrylate) and poly($\varepsilon$-caprolactone). Langmuir 24: 8272-8279. https://doi.org/10.1021/la800765y
  28. Spasova, M., L. Mespouille, O. Coulembier, D. Paneva, N. Manolova, I. Rashkov, and P. Dubois. 2009. Amphiphilic poly(D-or L-lactide)-b-poly(N,N-dimethylamino-2-ethyl methacrylate) block copolymers: Controlled synthesis, characterization, and stereocomplex formation. Biomacromolecules 10: 1217-1223. https://doi.org/10.1021/bm801515c

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