Membrane Journal (멤브레인)

The Membrane Society of Korea (한국막학회)
권호 표지

Characterization of Hyaluronic Acid Membrane Containing Lactic Acid

젖산이 결합된 히아루론산 막의 특성

  • Cheong Seong Ihl (Department of Chemical Engineering and Nano-Bio Technology, Hannam University) ;
  • Kwon Ji Young (Department of Chemical Engineering and Nano-Bio Technology, Hannam University)
  • 정성일 (한남대학교 나노생명화학공학과) ;
  • 권지영 (한남대학교 나노생명화학공학과)
  • Published : 2005.03.01
Download PDF
⟨ Previous Next ⟩

Abstract

The hyaluronic acid (HA) with excellent biocompatibility can be combined with the monomer polylactide with good biodegradability to produce biocompatible materials which can control the period of degradation in a human body. By freeze drying method, HA and the lactic acid, monomer of polylactide, or lactide, the ester dimer of polylactide, were crosslinked with crosslinking agent, l-ethyl-3-(3-dimethyl aminopropyl) carbodiimide. The analysis of infrared spectroscopy showed that the ester linkage was formed and the analysis of nuclear magnetic resonance (NMR) spectroscopy showed that the ester linkage was due to the reaction of lactic acid and HA. The conversion (6∼32%) and degree of crosslinking (4∼19%) increased but the selectivity was almost constant at 62% as the mole ratio of LA to HA increased from 1 to 10 in the crosslinking reaction. The brittleness became more pronounced and the rate of degradation became faster with more addition of lactic acid resulting from the higher ratio of LA to HA, and the swelling ratio was in the range of 500 to 2000%.

생체 적합성이 우수한 히아루론산과 생분해성이 우수한 폴리 락타이드의 모노머를 결합하여 인체내에서 분해속도를 조절할 수 있는 생체적합성이 우수한 생체 재료를 제조하고자 하였다. 냉동 건조법을 이용하여 히아루론산과 폴리락타이드의 모노머인 젖산 또는 이량체인 락타이드를 가교제 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide로 가교시켰다. 생성된 막을 적외선 흡수 분광법으로 분석한 결과 에스테르 결합이 생성됨을 확인하였고, 핵자기 공명 분광법으로 분석하여 이 에스테르 결합이 젖산의 반응 참여에 의한 것임을 확인하였다. 젖산과 히아루론산의 몰비를 1부터 10까지 증가시키면서 가교시킨 결과 젖산의 전화율(6∼32%)과 가교도(4∼l9%)는 증가하였으나, 반응에 참여한 젖산이 가교되는 선택도는 몰비에 관계없이 62% 정도로 일정하였다. 몰비가 커서 젖산이 많이 첨가되면 취성은 강해졌으나 생분해 속도는 빨라졌으며, 팽윤도는 500에서 2000% 범위의 값을 보였다.

Keywords

References

  1. Y. Tokita and A. Pkamoto, 'Degradation of hyaluronic acid-Kinetic study and thermodynamics', Eur. Polym. J, 32(8), 1011-1014 (1996) https://doi.org/10.1016/0014-3057(96)00019-5
  2. S. P. Zhong, D. Campoccia, P. J. Doherty, R. L. Willians, L. Benedetti, and D. F. Williams, 'Biodegradation of hyaluronic acid derivatives by hyaluronidase', Biomaterials, 15, 359-368 (1994) https://doi.org/10.1016/0142-9612(94)90248-8
  3. G. D. Prestwitch, D. M. Marecak, and J. F. Marecek, 'Controlled chemical modification of hyaluronin acid: synthesis, applications, and biodegradation of hydrazide derivatives', J. Control. Rel., 53, 93-103 (1998) https://doi.org/10.1016/S0168-3659(97)00242-3
  4. Y. Luo, K. R. Kirker, and G. D. Prestwich, 'Crosslinked hyaluronic acid hydrogel films: new biomaterials for drug delivery', J. Control. Rel., 69, 169-184 (2000) https://doi.org/10.1016/S0168-3659(00)00300-X
  5. S. N. Park, H. J. Lee, K. H. Lee, and H. Suh, 'Characterization of porous collagen/hyaluronic acid scaffold modified by l-ethyl- 3-(3-dimethylaminopropyl) carbodiimide cross-linking', Biomaterials, 22, 1205 -1212 (2002)
  6. S. N. Park, H. J. Lee, K. H. Lee, and H. Suh, 'Biological characterization of EDC-crosslinked collagen-hyaluronic acid matrix in dermal tissue restoration', Biomaterials, 24, 1631-1641 (2003) https://doi.org/10.1016/S0142-9612(02)00550-1
  7. H. S. Nam, J. H. Kim, J. H. An, and D. J. Jung, 'Synthesis of Hyaluronic acid scaffold for tissue engineering and evaluation of its drug release behaviors', Polymer(Korea), 25(4), 476-485 (2001)
  8. P. A. Delco, M. Stefanetti, D. Pressato, S. Piana, M. Dona, and A. Pavesio, 'A novel hyaluronanbased gel in laparoscopic adhesion prevention: preclinical evaluation in an animal model', Fertil. Steril., 69, 318-323 (1998) https://doi.org/10.1016/S0015-0282(98)00496-8
  9. J. A. Hunt, H. N. Joshi, V. J. Stella, and E. M. Topp, 'Diffusion and drug release in polymer films prepared from ester derivatives of hyaluronic acid', J. Control. Rel., 12, 159-169 (1990) https://doi.org/10.1016/0168-3659(90)90092-8
  10. L. Benedetti, R. Cortivo, T. Berti, A. Berti, F. Pea, M. Marzzo, M. Moras, and G. Abatangel, 'Biocompatibility and biodegradation of different hyaluronan derivatives (Hyaff) implanted in rats', Biomateials, 14, 1154-1160 (1993)
  11. J. Aigner, J. Tegeler, P. Hutzler, D. Campoccia, A. Pavesio, C. Hammer, E. Kastenbauer, and A. Naumann, 'Cartilage tissue engineering with novel nonwoven structured biomaterial based on hyaluronic acid benzyl ester', J. Biomed. Mater. Res., 42, 172 -181 (1998) https://doi.org/10.1002/(SICI)1097-4636(199811)42:2<172::AID-JBM2>3.0.CO;2-M
  12. G. P. Chen, Y. Ito, Y. Imanishi, A. Magnani, S. Lamponi, and R. Barbucci, 'Photoimmobilization of sulfated hyaluronic acid for antithrombogenicity', Bioconjugate Chem., 8, 730-734 (1997) https://doi.org/10.1021/bc9700493
  13. N. E. Larsen, E. A. Leshchiner, E. G. Parent, and E. A. Balazs, Cosmetic and Pharmaceutical Applications of Polymer; C. G. Gebelein, Ed., pp. 147-157, Plenun Press, New York (1991)
  14. J. W. Bums, L. Burgess, K. Skinner, M. J. Colt, R. Rose, and M. P. Diamond, 'A hyaluronate based gel for the prevention of postsurgical adhesions: evaluation in two animal species', Fertil. Steril., 66, 814-821 (1996) https://doi.org/10.1016/S0015-0282(16)58642-7
  15. J. S. Lee, D. J. Choo, S. H. Kim, and Y. H. Kim, 'Synthesis and degradation property of star-shaped polylactide', Polymer(Korea), 22(6), 880-889 (1998)
  16. C. Grandfils, P. Flandroy, and R. Jerome, 'Control of the biodegradation rate of poly(DL-lactide) microparticles intended as chemoembolization materials', J. Control. Rel., 38, 109-122 (1996) https://doi.org/10.1016/0168-3659(95)00102-6
  17. H. Fukuzaki, M. Yoshida, M. Asano, and M. Kumakura, 'Synthesis of copoly(D,L-lactic acid) with relatively low molecular weight and in vitro degradation', Eur. Polym. J., 25(10), 1019-1026 (1989) https://doi.org/10.1016/0014-3057(89)90131-6
  18. S. Li, M. Tenon, H. Garreau, Christian Braud, and Michel Vert, 'Enzymatic degradation of stereocopolymers derived from L -, D,L - and mesolactides', Polym. Degradation and Stability, 67, 85 -90 (2000) https://doi.org/10.1016/S0141-3910(99)00091-9
  19. E. Milella, E. Brescia, C. Massaro, P. A. Ramires, M. R. Miglietta, V. Fiori, and P. Aversa, 'Physicochemical properties and degradability of nonwoven hyaluronan benzylic esters as tissue engineering scaffolds', Biomaterials, 23, 1053 -1063 (2002) https://doi.org/10.1016/S0142-9612(01)00217-4
  20. E. K. Choi, H. I. Kim, K. R. Park, and Y. C. No, 'Preparation and charaterization of PVA/PVP/PEG/ Chitosan hydrogels by freezing/thawing and radiation crosslinking', J. Korean Ind. Eng. Chem., 14(4), 505-510 (2003)