DOI QR코드

DOI QR Code

Development of Protein Delivery System using Pullulan Acetate Microspheres (PAM)

플루란 아세테이트 미립구를 이용한 단백질 전달 시스템 개발

  • Na, Kun (Division of Biotechnology, The Catholic University of Korea) ;
  • Choi, Hoo-Kyun (College of Pharmacy, Chosun University)
  • 나건 (가톨릭대학교 생명공학부 생명공학전공) ;
  • 최후균 (조선대학교 약학대학)
  • Published : 2006.04.20

Abstract

The aim of this study was to develop new protein/peptide depot system instead of poly(DL-lactic acid-coglycolic acid) (PLGA) microspheres. Pullulan was chemically modified by the addition of acetic anhydride (pullulan acetate; PA) and then investigated as new depot system for protein/peptide delivery. PA microspheres (PAM) with lysozyme as a model protein were prepared by w/o/w double emulsion method. The microspheres had a mean size of 10-50 mm with a spherical shape. The size distributions reduced with increasing the degree of acetylation. The loading efficiency of lysozyme was also increased. Lysozyme aggregation behavior in the microsphere was monitored to estimate the change of protein stability during preparation step. The ratios of protein aggregation in PAMs are lower than that of PLGA microsphere, in particular, PA 5 showed lowest as about 16%. The result indicated that the increase of acetylation suppressed the aggregation of protein. The release profiles of lysozyme from PAMs were significantly different. High acetylation effectively improved lysozyme release kinetics by reducing initial burst release and extending continuous release over a period of time. To check the effect of preservation for structural stability of lysozyme, the activity of lysozyme released from PA 5 was also observed. The activity of lysozyme was maintained almost 100% for 25 day. Therefore, PAM may become to a useful carrier for delivery of protein/peptide drugs, if it will be supported by biocompatibility and biodegradability results.

Keywords

References

  1. W.R. Gombotz and D.K. Pettit., Reviews: Biodegradable polymers for protein and peptide drug delivery, Bioconjugation, 6, 332-351 (1995) https://doi.org/10.1021/bc00034a002
  2. G. Crotts and T.G Park, Review: Protein delivery from poly(lactic-co-glycolic acid) biodegradable microspheres: release kinetics and stability issues, J. Microencapsul., 15, 699-713 (1998) https://doi.org/10.3109/02652049809008253
  3. J.A. Schrier and P.P. DeLuca, Recombinant human bone morphogenetic protein-2 binding and incorporation in PLGA microspheres delivery, Pharm. Dev. Technol., 4, 611-621 (1999) https://doi.org/10.1081/PDT-100101400
  4. H. Thakkar, R.K. Sharma, A.K. Mishra, K. Chuttani and R.R. Murthy, Albumin microspheres as carriers for the antiarthritic drug celecoxib, AAPS Pharm. Sci. Tech., 6(1), E65-73 (2005) https://doi.org/10.1208/pt060112
  5. B.W. Woo, G Jiang, Y.W. Jo and P.P. DeLuca , Preparation and characterization of a composite PLGA and poly (acryloyl hydroxyethyl starch) microsphere system for protein delivery, Pharm. Res., 18, 1600-1606 (2001) https://doi.org/10.1023/A:1013090700443
  6. M.A. McDonald and K.L. Watkin, Investigations into the physicochemical properties of dextran small particulate gadolinium oxide nanoparticles, Acad Radiol., 13(4), 421-7 (2006) https://doi.org/10.1016/j.acra.2005.11.005
  7. J. Pean, F. Boury, M. Wenier-Julienne, P. Menei, J. Proust and J. Benoit, Why does PEG 400 co-encapsulation improve NGF stability and release from PLGA biodegradable microspheres, Pharm. Res., 16, 1294-1299 (1999) https://doi.org/10.1023/A:1014818118224
  8. T. Ehtezazi, C. Washington and CD. Melia, First order release rate from porous PLA microspheres with limited exit holes on the exterior surface, J. Control. Release, 66, 27-38 (2000) https://doi.org/10.1016/S0168-3659(99)00255-2
  9. F. Boury, Tz. Ivanova, I. Panaiotov, J.E. Proust, A. Bois and J. Richou, Dilatational properties of adsorbed poly(D,L-lactide) and bovine serum albumin monolayers at the dichloromethane/water interface, Langmuir, 11, 1636-1644 (1995) https://doi.org/10.1021/la00005a036
  10. J. Goodwin, M. Braden, S. Downes and N.J. Marshall, Release of bioactive human growth hormone from a biodegradable material: Poly(g-caprolactone), J. Biomed. Mater. Res. 40, 204-213 (1998) https://doi.org/10.1002/(SICI)1097-4636(199805)40:2<204::AID-JBM5>3.0.CO;2-P
  11. Y.Y. Yang, H.H. Chia and T.S. Chung, Effect of preparation temperature on the characteristics and release profiles of PLGA microspheres containing protein fabricated by double-emulsion solvent extraction/evaporation method, J. Control. Release, 69, 81-96 (2000) https://doi.org/10.1016/S0168-3659(00)00291-1
  12. J.L. Cleland, O.L. Johnson, S. Putney and A.J.S. Jones, Recombinant human growth hormone poly(lactic-co-glycolic acid) microspheres formulation development, Adv. Drug Delivery Rev., 28, 71-84 (1997) https://doi.org/10.1016/S0169-409X(97)00051-3
  13. J.L. Cleland, M.F. Powell and S.J. Shire, The development of stable protein formulations: A close look at protein aggregation, deamidation, and oxidation, Crit. Rev. Ther. Drug. Carrier Syst., 10, 307-377 (1993)
  14. F.M. Richards. Protein stability: Still an unsolved problem, Cellular and Molecular Life Science, 53, 790-802 (1997) https://doi.org/10.1007/s000180050100
  15. S.D. Putney and P.A. Burke. Improving protein therapeutics with sustained-release formulations, Nat. Biotechnol., 16, 153-157(1998) https://doi.org/10.1038/nbt0298-153
  16. W. Wang. Review: Lyophilization and development of solid protein pharmaceuticals, Int. J. Pharm., 203, 1-60 (2000) https://doi.org/10.1016/S0378-5173(00)00423-3
  17. M. van de Weert, W.E. Hennink and W Jiskoot. Review Article: Protein instability in poly(lactic-go-glycolic acid) microparticles, Pharm. Res., 17, 1159-1167 (2000) https://doi.org/10.1023/A:1026498209874
  18. J. Wang, B.M. Wang and S.P. Schwendeman. Characterization of the initial burst release of a model peptide from poly(D,L-lactide-co-glycolide) microspheres, J. Control. Release, 82, 289-307 (2002) https://doi.org/10.1016/S0168-3659(02)00137-2
  19. G Zhu, S.R. Mallery and S.P. Schwendeman, Stabilization of proteins encapsulated in injectable poly(lactide-co-glycolide), Nat. Biotechnol., 18, 52-57 (2000) https://doi.org/10.1038/71916
  20. J. Kang and S.P. Schwendeman, Comparison of the effects of $Mg(OH)_2$ and sucrose on the stability of bovine serum albumin encapsulated in injectable poly(D,L-lactide-co-glycolide) implants, Biomaterials, 23, 239-245 (2002) https://doi.org/10.1016/S0142-9612(01)00101-6
  21. J.H. Kim, A. Taluja, K. Knutson, Y.H. Bae, Stability of bovine serum albumin complexed with PEG-poly(L-histidine) diblock copolymer in PLGA microspheres, J Control Release, 109, 86-100 (2005) https://doi.org/10.1016/j.jconrel.2005.09.016
  22. Y. Xi, K. Tabata, M. Uno, T. Yoshimoto, Y. Kishida, Y Sokawa and Ikada, Liver targeting of interferon though pullulan conjugation, Pharm Res., 13, 1846-1850 (1996) https://doi.org/10.1023/A:1016037225728
  23. T. Nishikawa, K. Akiyoshi and J. Sunamoto, Macromole-cular complexation between bovine serum albumin and self-aggregated hydrogel nanoparticle of hydrophobized polysaccharide, J. Am. Chem. Soc., 118, 6110-6115 (1996) https://doi.org/10.1021/ja953843c
  24. K. Na, E.S. Lee and Y.H. Bae. Adriamycin loaded pullulan acetate/sulfonamide conjugate nanoparticles responding to tumor pH: pH-dependent cell interaction, internalization and cytotoxicity in vitro, J. Control. Release, 87, 3-13 (2003) https://doi.org/10.1016/S0168-3659(02)00345-0
  25. K. Na, K.H. Lee and Y.H. Bae. pH-Sensitivity and pH-dependent interior structure change of Self-Assembled Hydrogel Nanoparticles of Pullulan Acetate/Oligo(methacryloyl sulfadimethoxine) (PA/OSDM) Conjugates, J. Control. Release, 97, 513-525 (2004) https://doi.org/10.1016/S0168-3659(04)00184-1
  26. K. Na, K.H. Park, S.W. Kim and Y.H. Bae, Self-aggregated hydrogel nanoparticles from curdlan derivatives: characterization, anti-cancer drug release and interaction with a hepatoma cell line (HepG2), J. Control. Release, 69, 225-236 (2000) https://doi.org/10.1016/S0168-3659(00)00256-X
  27. K. Na and Y.H. Bae, Self-assembled hydrogel nanoparticles responsive to tumor extracelluar pH from hydrophobized pullulan and sulfonamide conjugate; Characterization, aggregation and adriamycin release in vitro, Pharm. Res., 19, 681-688 (2002) https://doi.org/10.1023/A:1015370532543
  28. K. Na, T.B. Lee, K.-H. Park, E.-K. Shin and H.-K. Choi. Self-assembled nanoparticles of hydrophobically-modified polysaccharide bearing vitamin H as a targeted anti-cancer drug delivery system, Eur. J. Pharm. Sci., 18, 165-173 (2003) https://doi.org/10.1016/S0928-0987(02)00257-9
  29. C. Perez, P.D. Jesu's and K. Griebenow, Preservation of lysozyme structure and function upon encapsulation and release from poly(lactic-co-glycolic) acid microspheres prepared by the water-in-oil-in-water method, Int. J. Pharm. 248, 193-206 (2002) https://doi.org/10.1016/S0378-5173(02)00435-0