Poly(methyl vinyl ether-co-maleic acid) Hydrogels Containing Cyclodextrins and Tween 85 for Potential Application as Hydrophobic Drug Delivery Systems

  • Eneko Larrañeta
  • Juan Domínguez-Robles
  • Martha Coogan
  • Emma Heaney
  • Sarah A. Stewart
  • Raghu Raj Singh Thakur
  • Ryan F. Donnelly


Hydrogels have been extensively investigated as a platform for drug delivery. However, their use for the delivery of hydrophobic drugs has been limited by their incompatibility with hydrophobic drug molecules. The chemical modification of the structure of the hydrogels to include hydrophobic moieties has been proven to be a good alternative to increase the stability and solubility of hydrophobic drugs in the polymer matrix of the hydrogel. The inclusion of hydroxypropyl-β-cyclodextrins (HPBCD) and Tween® 85 (T85) within hydrogel matrices has the potential to improve hydrophobic drug loading and release. HPBCD have the ability to host hydrophobic drug molecules in their cone-like structure, forming inclusion complexes through host-guest interactions. On the other hand, T85 is an amphiphilic molecule and, consequently, has the potential to increase hydrophilic drug loading within the hydrogels. In the present work, a new type of hydrogel made from poly(methyl vinyl ether-co-maleic acid) (GAN) and poly(ethylene glycol) (PEG) containing T85 and HPBCD was synthesized for hydrophobic drug release. Hydrogels were based on GAN crosslinked (PEG) and HPBCD and/or T85 via an esterification in the solid state (solvent free). The synthesised hydrogels were characterised using Fourier transform infrared (FTIR) spectroscopy, swelling studies and contact angle measurements. The hydrogels showed swellings ranging from 140 to 180%. The inclusion of T85 in the hydrogels improved the wettability of the materials. On the other hand, the inclusion of HPBCD within the hydrogels decreased the wettability as the contact angle between the hydrogels and water increased with the HPBCD content. Finally, the materials were loaded with an ophthalmic drug, dexamethasone (DX). HPBC-containing hydrogels showed a higher DX uptake and, consequently, also a higher capacity of DX release. On the other hand, T85 containing hydrogels did not show any improvement over the hydrogels containing only GAN and PEG. The hydrogels were able to provide sustained DX release over periods of 6 h.


hydrogels hydrophobic drug delivery dexamethasone cyclodextrin polysorbate 


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  1. (1).
    E. Caló and V. V. Khutoryanskiy, Eur. Polym. J., 65, 252 (2015).CrossRefGoogle Scholar
  2. (2).
    N. Peppas, J. Hilt, A. Khademhosseini, and R. Langer, Adv Mater, 18, 1345 (2006).CrossRefGoogle Scholar
  3. (3).
    N. A. Peppas, P. Bures, W. Leobandung, and H. Ichikawa, Eur. J. Pharm. Biopharm., 50, 27 (2000).CrossRefGoogle Scholar
  4. (4).
    T. Hoare and D. Kohane, Polymer, 49, 1993 (2008).CrossRefGoogle Scholar
  5. (5).
    S. Chatterjee, P. C. L. Hui, and C. W. Kan, Polymers, 10, 480 (2018).CrossRefGoogle Scholar
  6. (6).
    L. S. Liu, J. Kost, F. Yan, and R. C. Spiro, Polymers, 4, 997 (2012).CrossRefGoogle Scholar
  7. (7).
    M. F. Akhtar, M. Hanif, and N. M. Ranjha, Saudi Pharm. J., 24, 554 (2016).CrossRefGoogle Scholar
  8. (8).
    E. Larrañeta and J. R. Isasi, Carbohydr. Polym., 102, 674 (2014).CrossRefGoogle Scholar
  9. (9).
    T. Li, B. Kumru, N. Al Nakeeb, J. Willersinn, and B. V. K. J. Schmidt, Polymers, 10, 576 (2018).CrossRefGoogle Scholar
  10. (10).
    I. Antoniuk, D. Kaczmarek, A. Kardos, I. Varga, and C. Amiel, Polymers, 10, 566 (2018).CrossRefGoogle Scholar
  11. (11).
    C. A. Estevez, J. R. Isasi, E. Larraneta, and I. Velaz, Beilstein J. Org. Chem., 10, 3127 (2014).CrossRefGoogle Scholar
  12. (12).
    E. Larrañeta, S. Stewart, M. Ervine, R. Al-Kasasbeh, and R. F. Donnelly, J. Funct. Biomater., 9, 13 (2018).CrossRefGoogle Scholar
  13. (13).
    M. McKenzie, D. Betts, A. Suh, K. Bui, L. D. Kim, and H. Cho, Molecules, 20, 20397 (2015).CrossRefGoogle Scholar
  14. (14).
    D. Gu, A. J. O’Connor, G. G. H. Qiao, and K. Ladewig, Expert Opin. Drug Deliv., 14, 879 (2017).CrossRefGoogle Scholar
  15. (15).
    A. Fahr and X. Liu, Expert Opin. Drug Deliv., 4, 403 (2007).CrossRefGoogle Scholar
  16. (16).
    M. Pekar, Front. Mater., 1, 35 (2015).Google Scholar
  17. (17).
    E. Larrañeta, M. Imízcoz, J. X. Toh, N. J. Irwin, A. Ripolin, A. Perminova, J. Domíguez-Robles, A. Rodríguez, and R. F. Donnelly, ACS Sustainable Chem. Eng., 6, 9037 (2018).CrossRefGoogle Scholar
  18. (18).
    K. H. Hong, Y. S. Jeon, D. J. Chung, and J. H. Kim, Macromol. Res., 18, 204 (2010).CrossRefGoogle Scholar
  19. (19).
    S. Shukla, A. K. Bajpai, and J. Bajpai, Macromol. Res., 11, 273 (2003).CrossRefGoogle Scholar
  20. (20).
    E. Larraneta, L. Barturen, M. Ervine, and R. F. Donnelly, Int. J. Pharm., 538, 147 (2018).CrossRefGoogle Scholar
  21. (21).
    G. Gonzalez-Gaitano, J. R. Isasi, I. Velaz, and A. Zornoza, Curr. Pharm. Des., 23, 411 (2017).CrossRefGoogle Scholar
  22. (22).
    E. M. Martin Del Valle, Process Biochem., 39, 1033 (2004).CrossRefGoogle Scholar
  23. (23).
    E. Larrañeta, C. Martínez-Ohárriz, I. Vélaz, A. Zornoza, R. Machín, and J. R. Isasi, J. Pharm. Sci., 103, 197 (2014).CrossRefGoogle Scholar
  24. (24).
    J. B. Xiao, X. Q. Chen, H. Z. Yu, and M. Xu, Macromol. Res., 14, 443 (2006).CrossRefGoogle Scholar
  25. (25).
    P. Ojer, L. Neutsch, F. Gabor, J. M. Irache, and A. López de Cerain, J. Biomed. Nanotechnol., 9, 1891 (2013).CrossRefGoogle Scholar
  26. (26).
    E. Larrañeta, M. Henry, N. J. Irwin, J. Trotter, A. A. Perminova, and R. F. Donnelly, Carbohydr. Polym., 181, 1194 (2018).CrossRefGoogle Scholar
  27. (27).
    E. M. Vicente-Perez, E. Larraneta, M. T. C. McCrudden, A. Kissenpfennig, S. Hegarty, H. O. McCarthy, and R. F. Donnelly, Eur. J. Pharm. Biopharm., 117, 400 (2017).CrossRefGoogle Scholar
  28. (28).
    L. Ruiz-Gaton, S. Espuelas, E. Larraneta, I. Reviakine, L. A. Yate, and J. M. Irache, Eur. J. Pharm. Sci., 118, 165 (2018).CrossRefGoogle Scholar
  29. (29).
    R. F. Donnelly, T. R. R. Singh, M. J. Garland, K. Migalska, R. Majithiya, C. M. McCrudden, P. L. Kole, T. M. T. Mahmood, H. O. McCarthy, and A. D. Woolfson, Adv. Funct. Mater., 22, 4879 (2012).CrossRefGoogle Scholar
  30. (30).
    J. Domínguez-Robles, M. S. Peresin, T. Tamminen, A. Rodríguez, E. Larrañeta, and A. S. Jääskeläinen, Int. J. Biol. Macromol., 115, 1249 (2018).CrossRefGoogle Scholar
  31. (31).
    M. Sclavons, P. Franquinet, V. Carlier, G. Verfaillie, I. Fallais, R. Legras, M. Laurent, and F. C. Thyrion, Polymer, 41, 1989 (2000).CrossRefGoogle Scholar
  32. (32).
    B. Yang, C. Wei, Y. Yang, Q. Wang, and S. Li, Drug Dev. Ind. Pharm., 44, 1417 (2018).CrossRefGoogle Scholar
  33. (33).
    M. C. Lin and T. F. Svitova, Optom.Vis. Sci., 87, 440 (2010).CrossRefGoogle Scholar
  34. (34).
    C. F. Komives, D. E. Osborne, and A. J. Russell, J. Phys. Chem., 98, 369 (1994).CrossRefGoogle Scholar
  35. (35).
    X. Li, Y. Zhao, K. Wang, L. Wang, X. Yang, and S. Zhu, PLoS One, 12, e0189778 (2017).CrossRefGoogle Scholar
  36. (36).
    J. F. dos Santos, C. Alvarez-Lorenzo, M. Silva, L. Balsa, J. Couceiro, J. J. Torres-Labandeira, and A. Concheiro, Biomaterials, 30, 1348 (2009).CrossRefGoogle Scholar
  37. (37).
    R. Machín, J. R. Isasi, and I. Vélaz, Carbohydr. Polym., 87, 2024 (2011).CrossRefGoogle Scholar
  38. (38).
    J. K. Kristinsson, H. Fridriksdottir, S. Thorisdottir, A. M. Sigurdardottir, E. Stefansson, and T. Loftsson, Invest. Ophthalmol. Vis. Sci., 37, 1199 (1996).Google Scholar
  39. (39).
    M. Argenziano, C. Dianzani, B. Ferrara, S. Swaminathan, A. Manfredi, E. Ranucci, R. Cavalli, and P. Ferruti, Gels, 3, 22 (2017).CrossRefGoogle Scholar
  40. (40).
    D. Lucio, J. M. Irache, M. Font, and M. C. Martinez-Oharriz, Int.J.Pharm., 530, 377 (2017).CrossRefGoogle Scholar
  41. (41).
    D. Lucio, J. M. Irache, M. Font, and M. C. Martinez-Oharriz, Int. J. Pharm., 519, 263 (2017).CrossRefGoogle Scholar
  42. (42).
    A. Beig, R. Agbaria, and A. Dahan, PLoS One, 8, e68237 (2013).CrossRefGoogle Scholar
  43. (43).
    A. Usayapant, A. H. Karara, and M. M. Narurkar, Pharm. Res., 8, 1495 (1991).CrossRefGoogle Scholar
  44. (44).
    R. Iacovino, J. V. Caso, F. Rapuano, A. Russo, M. Isidori, M. Lavorgna, G. Malgieri, and C. Isernia, Molecules, 17, 6056 (2012).CrossRefGoogle Scholar
  45. (45).
    J. Wang, Z. Zhu, X. Jin, Z. Li, Y. Shao, and Z. Shao, Polymers, 8, 93 (2016).CrossRefGoogle Scholar
  46. (46).
    R. Machín, J. R. Isasi, and I. Vélaz, Eur. Polym. J., 49, 3912 (2013).CrossRefGoogle Scholar
  47. (47).
    K. Kesavan, S. Kant, P. N. Singh, and J. K. Pandit, Curr. Eye Res., 36, 918 (2011).CrossRefGoogle Scholar
  48. (48).
    J. Kim, C. C. Peng, and A. Chauhan, J.Control.Release, 148, 110 (2010).CrossRefGoogle Scholar
  49. (49).
    A. Boone, A. Hui, and L. Jones, Eye Contact Lens, 35, 260 (2009).CrossRefGoogle Scholar
  50. (50).
    G. Guidi, T. C. Hughes, M. Whinton, M. A. Brook, and H. Sheardown, J. Biomater. Appl., 29, 222 (2014).CrossRefGoogle Scholar
  51. (51).
    D. Nguyen, A. Hui, A. Weeks, M. Heynen, E. Joyce, H. Sheardown, and L. Jones, Materials (Basel), 5, 684 (2012).CrossRefGoogle Scholar
  52. (52).
    K. M. Brothers, A. C. Nau, E. G. Romanowski, and R. M. Shanks, Cornea, 33, 1083 (2014).CrossRefGoogle Scholar
  53. (53).
    F. Bian, C. S. Shin, C. Wang, S. C. Pflugfelder, G. Acharya, and C. S. De Paiva, Invest. Ophthalmol. Vis. Sci., 57, 3222 (2016).CrossRefGoogle Scholar
  54. (54).
    Z. Zhang, X. Wei, J. Gao, Y. Zhao, Y. Zhao, L. Guo, C. Chen, Z. Duan, P. Li, and L. Wei, Int. J. Mol. Sci., 17, 411 (2016).CrossRefGoogle Scholar
  55. (55).
    M. Hamalainen, R. Nieminen, I. Uurto, J. P. Salenius, M. Kellomaki, J. Mikkonen, A. Kotsar, T. Isotalo, L. J. Teuvo Tammela, M. Talja, and E. Moilanen, Basic Clin. Pharmacol. Toxicol., 112, 296 (2013).CrossRefGoogle Scholar
  56. (56).
    K. Dong, Y. Dong, C. You, W. Xu, X. Huang, Y. Yan, L. Zhang, K. Wang, and J. Xing, Drug Deliv., 23, 174 (2016).CrossRefGoogle Scholar
  57. (57).
    N. T. Tung, V. T. Huyen, and S. C. Chi, Arch. Pharm. Res., 38, 1999 (2015).CrossRefGoogle Scholar
  58. (58).
    S. Zhang, J. Ermann, M. D. Succi, A. Zhou, M. J. Hamilton, B. Cao, J. R. Korzenik, J. N. Glickman, P. K. Vemula, L. H. Glimcher, G. Traverso, R. Langer, and J. M. Karp, Sci. Transl. Med., 7, 300ra128 (2015).CrossRefGoogle Scholar

Copyright information

© The Polymer Society of Korea and Springer Nature B.V. 2018

Authors and Affiliations

  • Eneko Larrañeta
    • 1
  • Juan Domínguez-Robles
    • 1
  • Martha Coogan
    • 1
  • Emma Heaney
    • 1
  • Sarah A. Stewart
    • 1
  • Raghu Raj Singh Thakur
    • 1
  • Ryan F. Donnelly
    • 1
  1. 1.Queens University Belfast, School of PharmacyBelfastUK

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