Preparation of Hyaluronic Acid Microspheres with Enhanced Physical Stability by Double Cross-link or Alginate

이중 가교제 또는 알긴산에 의해 물리적인 안정성이 향상된 히알루론산 마이크로입자의 제조

  • Kim, Dong-Hwan (College of Pharmacy, Seoul National University) ;
  • Song, Chung-Kil (College of Pharmacy, Seoul National University) ;
  • Balakrishnan, Prabagar (College of Pharmacy, Seoul National University) ;
  • Park, Chun-Geon (Department of Herbal Crop Research, National Institute of Horticultural & Herbal Science, RDA) ;
  • Choi, Ae-Jin (Department of Herbal Crop Research, National Institute of Horticultural & Herbal Science, RDA) ;
  • Chung, Suk-Jae (College of Pharmacy, Seoul National University) ;
  • Shim, Chang-Koo (College of Pharmacy, Seoul National University) ;
  • Kim, Dae-Duk (College of Pharmacy, Seoul National University)
  • 김동환 (서울대학교 약학대학 약제학과) ;
  • 송충길 (서울대학교 약학대학 약제학과) ;
  • ;
  • 박충근 (농촌진흥청 국립원예특작과학원 인삼특작부 약용작물과) ;
  • 최애진 (농촌진흥청 국립원예특작과학원 인삼특작부 약용작물과) ;
  • 정석재 (서울대학교 약학대학 약제학과) ;
  • 심창구 (서울대학교 약학대학 약제학과) ;
  • 김대덕 (서울대학교 약학대학 약제학과)
  • Received : 2010.10.21
  • Accepted : 2011.02.11
  • Published : 2011.02.28

Abstract

Hyaluronic acid (HA) is a natural polymer consisting of disaccharide units of D-glucuronic acid and N-acetyl-D-glucosamine. It has a great potential and success in cosmetic and biomedical applications. However, native HA is highly soluble and easily metabolized by enzymes such as hyaluronidase. Thus, various studies have been reported on modifying the physicochemical properties of HA, while maintaining its biocompatibility. For controlled drug delivery, many trials for fabricating HA microspheres were achieved under chemical reaction. The HA microspheres fabricated to improve the physical stability of HA using adipic acid dihydrazide (ADH) by cross-linking reaction has been reported earlier, however it lacks the desired physical stability and rapidly decomposes by swelling or enzymes. Therefore, we prepared double cross-linked HA microspheres (DC-HA microspheres) and alginate containing HA microspheres (AC-HA microspheres) to enhance its physicochemical properties. DC-HA microspheres were prepared using trisodium trimetaphosphate (STMP) under crosslinking reaction after ADH cross-linking reaction. AC-HA microspheres were prepared by adding alginate as a networking polymer. These microspheres were characterized by morphology, particle size, zeta potential, stability against hyaluronidase. Results showed that the DC-HA and AC-HA microspheres are more stable than that of HA microspheres.

Keywords

References

  1. Laurent, T., Laurent, U. and Fraser, J. R. : Functions of hyaluronan. Ann. Rheum. Dis. 54, 429 (1995). https://doi.org/10.1136/ard.54.5.429
  2. Laurent, T., Laurent, U. and Fraser, J. R. : The structure and function of hyaluronan: An overview. Immunol. Cell Biol. 74, A1 (1996). https://doi.org/10.1038/icb.1996.32
  3. Chen, W. and Abatangelo, G. : Functions of hyaluronan in wound repair. Wound Repair Regen. 7, 79 (1999). https://doi.org/10.1046/j.1524-475X.1999.00079.x
  4. Scott, J. : Extracellular matrix, supramolecular organisation and shape. J. Anat. 187, 259 (1995).
  5. Collis, L., Hall, C., Lange, L., Ziebell, M., Prestwich, R. and Turley, E. : Rapid hyaluronan uptake is associated with enhanced motility: implications for an intracellular mode of action. FEBS Letters 440, 444 (1998). https://doi.org/10.1016/S0014-5793(98)01505-1
  6. Toole, B. : Hyaluronan in morphogenesis, Semin. Cell Dev. Biol. 12, 79 (2001). https://doi.org/10.1006/scdb.2000.0244
  7. Gerdinand, B. and Hallgren, R. : Dynamic role of hyaluronan (HYA) in connective tissue activation and inflammation. J. Intern. Med. 242, 49 (1997). https://doi.org/10.1046/j.1365-2796.1997.00173.x
  8. Kim, A., Checla, D. M. and Chen, W. : Characterization of DNAhyaluronan matrix for sustained gene transfer. J. Control. Release 90, 81 (2003). https://doi.org/10.1016/S0168-3659(03)00175-5
  9. Freed, L. E., Vunjak-Novakovic, G., Biron, R. J., Eagles, D. B., Lenov, D. C., Barlow, S. K. and Langer, R. : Biodegradable polymer scaffolds for tissue engineering. Biotechnology 12, 689 (1994). https://doi.org/10.1038/nbt0794-689
  10. Kang, J. Y., Chung, C. W., Sung, J. H., Park, B. S., Choi, J. Y., Lee, S. J., Choi, B. C., Shim, C. K., Chung, S. J. and Kim, D. D. : Novel porous matrix of hyaluronic acid for the threedimensional culture of chondrocytes. Int. J. Pharm. 369, 114 (2009). https://doi.org/10.1016/j.ijpharm.2008.11.008
  11. Yunand, Y. : Hyaluronan microspheres for sustained gene delivery and site-specific targeting. Biomaterials 25, 147 (2004). https://doi.org/10.1016/S0142-9612(03)00467-8
  12. Zhao, X. B., Fraser, J. E., Alexander, C., Lockett, C. and White, B. J. : Synthesis and characterization of a novel double crosslinked hyaluronan hydrogel. J. Mater. Sci. 13, 11 (2002).
  13. Zawko, S., Suri, S., Truong, Q. and Schmidt, C. : Photopatterned anisotropic swelling of dual-crosslinked hyaluonic acid hydrogels. Acta Biomater. 5, 14 (2009). https://doi.org/10.1016/j.actbio.2008.09.012
  14. Dulong, V. : Hyaluronan-based hydrogels particles prepared by crosslinking with trisodium trimetaphosphate. Synthesis and characterization. Carbohydr. Polym. 57, 1 (2004). https://doi.org/10.1016/j.carbpol.2003.12.006
  15. Scott, A., Zawko, Shalu S., Quan, T. and Chrestine, E. Schmidt : Photopatterned anisotropic swelling of dual cross-linked hyaluronic acid hydrogels. Acta Biomater. 5, 14 (2009). https://doi.org/10.1016/j.actbio.2008.09.012
  16. Zhao, X. B., Fraser, J. E., Alexander, C., Lockett, C. and White, B. J. : Synthesis and characterization of a novel double crosslinked hyaluronan hydrogel. J. Mater. Sci. 13, 11 (2002).
  17. Cheon, J. W., Shim, C. K., Chung, S. J. and Kim, D. D. : Effect of tripolyphosphate (TPP) on the controlled release of cyclosporin a from chitosan-coated lipid microparticles. J. Kor. Pharm. Sci. 39, 59 (2009).