DOI QR코드

DOI QR Code

Sustained Release of Anthocyanin from Porous Poly(lactic-co-glycolide) Microsparticles Developed for the Treatment of Chronic Obstructive Pulmonary Disease

  • Yoo, Na-Young (Division of Biotechnology, The Catholic University of Korea) ;
  • Baik, Hye-Jung (Division of Biotechnology, The Catholic University of Korea) ;
  • Lee, Bo-Reum (Division of Biotechnology, The Catholic University of Korea) ;
  • Youn, Yu-Seok (College of Pharmacy, Pusan National University) ;
  • Oh, Kyung-Taek (College of Pharmacy, Chung-Ang University) ;
  • Lee, Eun-Seong (Division of Biotechnology, The Catholic University of Korea)
  • Received : 2010.07.08
  • Accepted : 2010.07.31
  • Published : 2010.08.20

Abstract

This study was to fabricate the porous poly(lactide-co-glycolide) (PLGA) microparticles with anthocyanin (as a model antioxidant) for pulmonary drug delivery. The highly porous PLGA microparticles were prepared by the waterin-oil-in-water ($W_1/O/W_2$) multi-emulsion method, followed by the decomposition of ammonium bicarbonate (AB) in $W_1$ phase to the base of ammonia, carbon dioxide and water vapor at $50^{\circ}C$, making a porous structure in PLGA microparticles. Herein, hyaluronate (HA), a viscous polysaccharide, was incorporated in the porous microparticles for sustained anthocyanin release. In in vitro release studies, the anthocyanin release from the porous microparticles with HA continued up to 24 hours, while the porous microparticles without HA released 80 wt.% of encapsulated anthocyanin within 2 hours. In addition, these microparticle are expected to be effectively deposited at a lung epithelium due to its high porosity (low density) and avoid alveolar macrophage's uptake in the lung due to its large particle size. We believe that this system has a great pharmaceutical potential as a long acting antioxidant for relieving the oxidative stress in chronic obstructive pulmonary disease (COPD).

Keywords

References

  1. Agu, R.U., Ugwoke, M.I., Armand, M., Kinget, R., Verbeke, N., 2001. The lung as a route for systemic delivery of therapeutic proteins and peptides. Respir. Res. 2, 198-209. https://doi.org/10.1186/rr58
  2. Bot, A.I., Tarara, T.E., Smith, D.J., Bot, S.R., Woods, C.M., Weers J.G., 2000. Novel lipid-based hollow-porous microparticles as a platform for immunoglobulin delivery to the respiratory tract. Pharm. Res. 17, 275-283. https://doi.org/10.1023/A:1007544804864
  3. Dunbar, C., Scheuch, G., Sommerer, K., DeLong, M., 2002. In vitro and in vivo dose delivery characteristics of large porous particles for inhalation. Int. J. Pharm. 245, 179-189. https://doi.org/10.1016/S0378-5173(02)00349-6
  4. Edwards, D.A., Hanes, J., Caponetti, G., Hrkach, J., Ben-Jebria, A., Eskew, M.L., Mintzes, J., Deaver, D., Lotan, N., Langer, R., 1997. Large porous particles for pulmonary drug delivery. Science 276, 1868-1871. https://doi.org/10.1126/science.276.5320.1868
  5. Gauliard, B., Grieve, D., Wilson, R., Crozier, A., Jenkins, C., Mullen, W.D., Lean, M., 2008. The effects of dietary phenolic compounds on cytokine and antioxidant production by A549 cells. J. Med. Food 11, 382-384. https://doi.org/10.1089/jmf.2007.593
  6. Hahn, S.K., Kim, S.J., Kim, M.J., Kim, D.H., 2004. Characterization and in vivo study of sustained-release formulation of human growth hormone using sodium hyaluronate. Pharm. Res. 21, 1374-1381. https://doi.org/10.1023/B:PHAM.0000036910.41224.de
  7. Jafari, M., Ghanei, M., 2010. Evaluation of plasma, erythrocytes, and bronchoalveolar lavage fluid antioxidant defense system in sulfur mustard-injured patients. Clin. Toxicol (Phila). 48, 184-192. https://doi.org/10.3109/15563651003623297
  8. Kim, H.K., Chung, H.J., Park, T.G., 2006. Biodegradable polymeric microspheres with “open/closed” pores for sustained release of human growth hormone. J. Control. Release 112, 167-174. https://doi.org/10.1016/j.jconrel.2006.02.004
  9. Koushik, K., Dhanda, D.S., Cheruvu, N.P.S., Kompella, U.B., 2004. Pulmonary delivery of deslorelin: large-porous PLGA particles and $HP{\beta}CD$ complexes. Pharm. Res. 21, 1119-1126. https://doi.org/10.1023/B:PHAM.0000032997.96823.88
  10. Kwon, M.J., Bae, J.H., Kim, J.J., Na, K., Lee, E.S., 2007. Long acting porous microparticle for pulmonary protein delivery. Int. J. Pharm. 333, 5-9. https://doi.org/10.1016/j.ijpharm.2007.01.016
  11. Lee, E.S., Kwon, M.J., Na, K., Bae, J.H., 2007a. Protein release behavior from porous microparticle with lysozyme/hyaluronate ionic complex. Colloids Surf. B 55, 125-130. https://doi.org/10.1016/j.colsurfb.2006.11.024
  12. Lee, E.S., Kwon, M.J., Lee, H., Kim, J.J., 2007b. Stabilization of protein encapsulated in poly(lactide-co-glycolide) microsphere by novel viscous S/W/O/W method. Int. J. Pharm. 331, 27-37. https://doi.org/10.1016/j.ijpharm.2006.09.008
  13. Lee, W., Thomas, P.S., 2009. Oxidative stress in COPD and its measurement through exhaled breath condensate. Clin. Transl. Sci. 2, 150-155. https://doi.org/10.1111/j.1752-8062.2009.00093.x
  14. Musante, C.J., Schroeter, J.D., Rosati, J.A., Crowder, T.M., Hickey, A.J., Martonen, T.B., 2002. Factors affecting the deposition of inhaled porous drug particles. J. Pharm. Sci. 91, 1580-1590.
  15. Oh, K.T., Kim, D., You, H.H., Ahn, Y.S., Lee, E.S., 2009. pH-sensitive properties of surface charge-switched multifunctional polymeric micelle. Int. J. Pharm. 376, 134-140. https://doi.org/10.1016/j.ijpharm.2009.04.021
  16. Okumu, F.W., Dao, L.N., Fielder, P.J., Dybdal, N., Brooks, D., Sane, S., Cleland, J.L., 2002. Sustained delivery of human growth hormone from a novel gel system: SABERTM. Biomaterials 23, 4353-4358. https://doi.org/10.1016/S0142-9612(02)00174-6
  17. Park, H.I., Kim, H.U., Lee, E.S., Lee, K.C., Youn, Y.S., 2009. Preparation of highly porous poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres. J. Kor. Pharm. Sci. 39, 167-171. https://doi.org/10.4333/KPS.2009.39.3.167
  18. Rahman, I., 2008. Antioxidant therapeutic advances in COPD. Ther. Adv. Respir. Dis. 2, 351-374. https://doi.org/10.1177/1753465808098224
  19. Ungaro, F., De Rosa, G., Miro, A., Quaglia, F., La Rotonda, M.I., 2006. Cyclodextrins in the production of large porous particles: development of dry powders for the sustained release of insulin to the lungs. Eur. J. Pharm. Sci. 28, 423-432. https://doi.org/10.1016/j.ejps.2006.05.005
  20. Varani, K., Caramori, G., Vincenzi, F., Tosi, A., Barczyk, A., Contoli, M., Casolari, P., Triggiani, M., Hansel, T., Leung, E., Maclennan, S., Barnes, P.J., Chung, K.F., Adcock, I., Papi, A., Borea, P.A., 2010. Oxidative/Nitrosative stress selectively altered A(2B) adenosine receptors in chronic obstructive pulmonary disease. FASEB J. 24, 1192-1204. https://doi.org/10.1096/fj.09-139485
  21. Wang, H., Nair, M.G., Strasburg, G.M., Chang, Y.C., Booren, A. M., Gray, J.I., DeWitt, D.L., 1999. Antioxidant and antiinflammatory activities of anthocyanins and their aglycon, cyanidin, from tart cherries. J. Nat. Prod. 62, 294-296. https://doi.org/10.1021/np980501m