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Poly(Dimethylaminoethyl Methacrylate)-Based pH-Responsive Hydrogels Regulate Doxorubicin Release at Acidic Condition

  • Lee, Seung-Hun (Department of Engineering Chemistry, Chungbuk National University) ;
  • You, Jin-Oh (Department of Engineering Chemistry, Chungbuk National University)
  • Received : 2015.05.02
  • Accepted : 2015.05.20
  • Published : 2015.06.30

Abstract

Stimuli-responsive biomaterials that alter their function through sensing local molecular cues may enable technological advances in the fields of drug delivery, gene delivery, actuators, biosensors, and tissue engineering. In this research, pH-responsive hydrogel which is comprised of dimethylaminoethyl methacylate (DMAEMA) and 2-hydroxyethyl methacrylate (HEMA) was synthesized for the effective delivery of doxorubicin (Dox) to breast cancer cells. Cancer and tumor tissues show a lower extracellular pH than normal tissues. DMAEMA/HEMA hydrogels showed significant sensitivity by small pH changes and each formulation of hydrogels was examined by scanning electron microscopy, mechanical test, equilibrium mass swelling, controlled Dox release, and cytotoxicity. High swelling ratios and Dox release were obtained at low pH buffer condition, low cross-linker concentration, and high content of DMAEMA. Dox release was accelerated to 67.3% at pH 5.5 for 6-h incubation at $37^{\circ}C$, while it was limited to 13.8% at pH7.4 at the same time and temperature. Cell toxicity results to breast cancer cells indicate that pH-responsive DMAEMA/HEMA hydrogels may be used as an efficient matrix for anti-cancer drug delivery with various transporting manners. Also, pH-responsive DMAEMA/HEMA hydrogels may be useful in therapeutic treatment which is required a triggered release at low pH range such as gene delivery, ischemia, and diabetic ketoacidosis.

Keywords

References

  1. S. Cui, Y. Hu, Z. Huang, C. Ma, L. Yu, X. Hu, Int.J. Therm. Sci. 79 (2014) 276-282. https://doi.org/10.1016/j.ijthermalsci.2014.01.015
  2. D.P. Huynh, G.J. Im, S.Y. Chae, K.C. Lee, D.S. Lee, J. Control. Release 137 (2009) 20-24. https://doi.org/10.1016/j.jconrel.2009.02.021
  3. N. Zalachas, S. Cai, Z. Suo, Y. Lapusta, Int. J. Solids. Struct. 50 (2013) 920-927. https://doi.org/10.1016/j.ijsolstr.2012.11.015
  4. Y. Hu, J.O. You, D.T. Auguste, Z. Suo, J.J. Vlassak, J. Mater. Res. 27 (2012) 152-160. https://doi.org/10.1557/jmr.2011.368
  5. J. Liu, J. Nie, Y. Zhao, Y. He, J. Photoch. Photobio. A 211 (2010) 20-25. https://doi.org/10.1016/j.jphotochem.2010.01.016
  6. H. Li, Z. Yuan, K.Y. Lam, H.P. Lee, J. Chen, J. Hanes, J. Fu, Biosens. Bioelectron. 19 (2004) 1097-1107. https://doi.org/10.1016/j.bios.2003.10.004
  7. X.-W. Liu, S. Zhu, S.-R. Wu, P. Wang, G.-Z. Han, Colloid Surface A 417 (2013) 140-145. https://doi.org/10.1016/j.colsurfa.2012.09.044
  8. A.M. Lowman, M. Morishita, M. Kajita, T. Nagai, N.A. Peppas, J. Pharm. Sci. 88 (1999) 933-937. https://doi.org/10.1021/js980337n
  9. J.O. You, D.T. Auguste, Nano Lett. 9 (2009) 4467-4473. https://doi.org/10.1021/nl902789s
  10. X. Gao, Y. Cao, X. Song, Z. Zhang, X. Zhuang, C. He, X. Chen, Macromol. Biosci. 14 (2014) 565-575. https://doi.org/10.1002/mabi.201300384
  11. N.I. Georgiev, A.M. Asiri, A.H. Qusti, K.A. Alamry, V.B. Bojinov, Sensor. Actuat. B-Chem. 190 (2014) 185-198. https://doi.org/10.1016/j.snb.2013.08.074
  12. S.W. Jang, J.W. Lee, D.S. Ryu, M. Son, M.J. Kang, Int. J. Biol. Macromol. 70C (2014) 174-178.
  13. N. Solomko, O. Budishevska, S. Voronov, K. Landfester, A. Musyanovych, Macromol. Biosci. 14 (2014) 1076-1083. https://doi.org/10.1002/mabi.201300512
  14. S.S. Halacheva, D.J. Adlam, E.K. Hendow, T.J. Freemont, J. Hoyland, B.R. Saunders, Biomacromolecules 15 (2014) 1814-1827. https://doi.org/10.1021/bm5002069
  15. P. Yang, D. Li, S. Jin, J. Ding, J. Guo, W. Shi, C. Wang, Biomaterials 35 (2014) 2079-2088. https://doi.org/10.1016/j.biomaterials.2013.11.057
  16. J.O. You, D.T. Auguste, Biomaterials 31 (2010) 6859-6866. https://doi.org/10.1016/j.biomaterials.2010.04.048
  17. Y. Tian, Chinese Chem. Lett. 19 (2008) 1111-1114. https://doi.org/10.1016/j.cclet.2008.05.040
  18. S. Peppicelli, F. Bianchini, L. Calorini, Cancer metastasis Rev. 33 (2014) 823-832. https://doi.org/10.1007/s10555-014-9506-4
  19. S. Quader, H. Cabral, Y. Mochida, T. Ishii, X. Liu, K. Toh, H. Kinoh, Y. Miura, N. Nishiyama, K. Kataoka, J. Control. Release 188 (2014) 67-77. https://doi.org/10.1016/j.jconrel.2014.05.048
  20. A.L. Daniel-da-Silva, L. Ferreira, A.M. Gil, T. Trindade, J. Colloid Interface Sci. 355 (2011) 512-517. https://doi.org/10.1016/j.jcis.2010.12.071
  21. J.O. You, D.T. Auguste, Biomaterials 29 (2008) 1950-1957. https://doi.org/10.1016/j.biomaterials.2007.12.041
  22. F.R. Gruijil, H.J. Kranen, L.H.F. Mullenders, J. Photoch. Photobio. B 63 (2001) 19-27. https://doi.org/10.1016/S1011-1344(01)00199-3
  23. X. Zhang, K. Matyjaszewski, Macromolecules 32 (1999) 1763-1766. https://doi.org/10.1021/ma981332f
  24. S. Brahim, D. Narinesingh, A. Guiseppi-Elie, Biomacromolecules 4 (2003) 1224-1231. https://doi.org/10.1021/bm034048r
  25. Y. Li, K. Xiao, W. Zhu, W. Deng, K.S. Lam, Adv. Drug Deliv. Rev. 66 (2014) 58-73. https://doi.org/10.1016/j.addr.2013.09.008
  26. R.P. Johnson, S. Uthaman, J.V. John, M.S. Heo, I.K. Park, H. Suh, I. Kim, Macromol. Bio. 14 (2014) 1239-1248. https://doi.org/10.1002/mabi.201400071
  27. G. Slaughter, J. Sunday, IEEE Sens. J. 14 (2014) 1573-1576. https://doi.org/10.1109/JSEN.2014.2298359
  28. N. Ramalingam, T.S. Natarajan, S. Rajiv, J. Biomed. Mater. Res. A 103 (2014) 16-24.
  29. A. Gabizon, H. Shmeeda, T. Grenader, Eur. J. Pharm. Sci. 45 (2012) 388-398. https://doi.org/10.1016/j.ejps.2011.09.006
  30. J.O. You, P. Guo, D.T. Auguste, Angew. Chem. Int. Edit. 52 (2013) 4141-4146. https://doi.org/10.1002/anie.201209804
  31. G.D. Kang, S.H. Cheon, S.C. Song, Int. J. Pharm. 319 (2006) 29-36. https://doi.org/10.1016/j.ijpharm.2006.03.032
  32. L. Mu, S.S. Feng, J. Contorl. Release 86 (2003) 33-48. https://doi.org/10.1016/S0168-3659(02)00320-6