Polymer Bulletin

, Volume 75, Issue 3, pp 1075–1099 | Cite as

Preparation and characterization of alginate-PVA-based semi-IPN: controlled release pH-responsive composites

  • Ikrima Khalid
  • Mahmood Ahmad
  • Muhammad Usman Minhas
  • Kashif Barkat
Original Paper
  • 89 Downloads

Abstract

The objective was to develop naturally derived polymer-based hydrogels with high mechanical strength and a controlled delivery of drug for extended period of time. Here, we report the fabrication of chemically cross-linked polyvinyl alcohol-graft-poly(acrylic acid)/sodium alginate hydrogel as a semi-interpenetrating polymer network (SIPN). For the preparation of SIPN hydrogels, SA and PVA were cross-linked with AA monomer in the presence of co-monomer EGDMA through free-radical polymerization reaction, using APS as an initiator. Loxoprofen sodium was loaded as a model drug. FTIR, XRD, TGA, and DSC were performed for the characterization of copolymer. Surface morphology was studied by SEM. Swelling studies were carried out at low and higher pH to evaluate pH-dependent swelling of formed SIPN hydrogels. FTIR, XRD, TGA, and DSC studies confirmed the formation of a new copolymer. Developed SIPN hydrogels showed maximum swelling, drug loading, and drug release at pH 7.4 while low at pH 1.2. Moreover, formulations with higher AA contents showed maximum swelling at 7.4 pH. High drug loading and higher drug release have been observed at pH 7.4. In vitro release profile of loxoprofen sodium was found dependent on pH, concentration of monomers, and cross-linking agent. Gel% and yield% for the prepared SIPN hydrogels were determined and found that gel% or yield% is directly proportional to the concentration of polymers, i.e., SA and PVA, due to their behavior as macromolecule radicals for monomer. The results from FTIR analysis showed that both SA and PVA react with the acrylic acid monomer during the polymerization process and result into the formation of SIPN. The formation of semi-IPN structure significantly improved the surface morphology of SIPN hydrogels as evident by SEM, which corresponds to their improved swelling ability and mechanical strength. Drug release mechanism from the formed SIPN was explained by kinetic modeling and found that first-order, Higuchi model, and Korsmeyer–Peppas model are the best fit models to explain drug release from hydrogels. Conclusively, prepared hydrogels were highly pH-responsive and showed good mechanical strength and time-dependent drug release. SIPN hydrogels could be a potential carrier network for controlled delivery of loxoprofen sodium for extended period of time.

Keywords

Sodium alginate Polyvinyl alcohol Acrylic acid Semi-interpentrating network Hydrogel pH-responsive Loxoprofen sodium 

References

  1. 1.
    Garcıa D, Escobar J, Bada N, Casquero J, Hernáez E, Katime I (2004) Synthesis and characterization of poly(methacrylic acid) hydrogels for metoclopramide delivery. Eur Polym J 40(8):1637–1643CrossRefGoogle Scholar
  2. 2.
    Hoare TR, Kohane DS (2008) Hydrogels in drug delivery: progress and challenges. Polymer 49(8):1993–2007CrossRefGoogle Scholar
  3. 3.
    Hennink W, Van Nostrum CF (2012) Novel crosslinking methods to design hydrogels. Adv Drug Deliv Rev 64:223–236CrossRefGoogle Scholar
  4. 4.
    Buwalda SJ, Boere KW, Dijkstra PJ, Feijen J, Vermonden T, Hennink WE (2014) Hydrogels in a historical perspective: from simple networks to smart materials. J Control Release 190:254–273CrossRefGoogle Scholar
  5. 5.
    Ratner BD, Hoffman AS (1976) Synthetic hydrogels for biomedical applications. Hydrogels Med Relat Appl 31:1–36CrossRefGoogle Scholar
  6. 6.
    Hamidi M, Azadi A, Rafiei P (2008) Hydrogel nanoparticles in drug delivery. Adv Drug Deliv Rev 60(15):1638–1649CrossRefGoogle Scholar
  7. 7.
    Burek M, Czuba ZP, Waskiewicz S (2014) Novel acid-degradable and thermo-sensitive poly(N-isopropylacrylamide) hydrogels cross-linked by α, α-trehalose diacetals. Polymer 55(25):6460–6470CrossRefGoogle Scholar
  8. 8.
    Zhao C, Zhuang X, He P, Xiao C, He C, Sun J, Chen X, Jing X (2009) Synthesis of biodegradable thermo-and pH-responsive hydrogels for controlled drug release. Polymer 50(18):4308–4316CrossRefGoogle Scholar
  9. 9.
    Yan B, Boyer J-C, Habault D, Branda NR, Zhao Y (2012) Near infrared light triggered release of biomacromolecules from hydrogels loaded with upconversion nanoparticles. J Am Chem Soc 134(40):16558–16561CrossRefGoogle Scholar
  10. 10.
    Tomatsu I, Peng K, Kros A (2011) Photoresponsive hydrogels for biomedical applications. Adv Drug Deliv Rev 63(14):1257–1266CrossRefGoogle Scholar
  11. 11.
    Némethy Á, Solti K, Kiss L, Gyarmati B, Deli MA, Csányi E, Szilágyi A (2013) pH-and temperature-responsive poly(aspartic acid)-l-poly(N-isopropylacrylamide) conetwork hydrogel. Eur Polym J 49(9):2392–2403CrossRefGoogle Scholar
  12. 12.
    Gyarmati B, Némethy Á, Szilágyi A (2014) Reversible response of poly(aspartic acid) hydrogels to external redox and pH stimuli. RSC Adv 4(17):8764–8771CrossRefGoogle Scholar
  13. 13.
    Maitz MF, Freudenberg U, Tsurkan MV, Fischer M, Beyrich T, Werner C (2013) Bio-responsive polymer hydrogels homeostatically regulate blood coagulation. Nat Commun 4(2168):1–7Google Scholar
  14. 14.
    Peppas NA, Hilt JZ, Khademhosseini A, Langer R (2006) Hydrogels in biology and medicine: from molecular principles to bionanotechnology. Adv Mater 18(11):1345–1360CrossRefGoogle Scholar
  15. 15.
    Bhattarai N, Gunn J, Zhang M (2010) Chitosan-based hydrogels for controlled, localized drug delivery. Adv Drug Deliv Rev 62(1):83–99CrossRefGoogle Scholar
  16. 16.
    Sperling LH (2012) Interpenetrating polymer networks and related materials, vol 6. Springer Science & Business Media, BerlinGoogle Scholar
  17. 17.
    Rao KK, Naidu BVK, Subha M, Sairam M, Aminabhavi T (2006) Novel chitosan-based pH-sensitive interpenetrating network microgels for the controlled release of cefadroxil. Carbohydr Polym 66(3):333–344CrossRefGoogle Scholar
  18. 18.
    Kulkarni RV, Sreedhar V, Mutalik S, Setty CM, Sathya B (2010) Interpenetrating network hydrogel membranes of sodium alginate and poly vinyl alcohol for controlled release of prazosin hydrochloride through skin. Int J Biol Macromol 47(4):520–527CrossRefGoogle Scholar
  19. 19.
    Pescosolido L, Vermonden T, Malda J, Censi R, Dhert WJ, Alhaique F, Hennink WE, Matricardi P (2011) In situ forming IPN hydrogels of calcium alginate and dextran-HEMA for biomedical applications. Acta Biomater 7(4):1627–1633CrossRefGoogle Scholar
  20. 20.
    Wen C, Lu L, Li X (2014) Mechanically robust gelatin-alginate IPN hydrogels by a combination of enzymatic and ionic crosslinking approaches. Macromol Mater Eng 299(4):504–513CrossRefGoogle Scholar
  21. 21.
    Zhang GQ, Zha LS, Zhou MH, Ma JH, Liang BR (2005) Preparation and characterization of pH-and temperature-responsive semi-interpenetrating polymer network hydrogels based on linear sodium alginate and crosslinked poly(N-isopropylacrylamide). J Appl Polym Sci 97(5):1931–1940CrossRefGoogle Scholar
  22. 22.
    Kim JH, Lee SB, Kim SJ, Lee YM (2002) Rapid temperature/pH response of porous alginate-g-poly(N-isopropylacrylamide) hydrogels. Polymer 43(26):7549–7558CrossRefGoogle Scholar
  23. 23.
    Sohail M, Ahmad M, Minhas MU, Liaqat A, Munir A, Khalid I (2014) Synthesis and characterization of graft PVA composites for controlled delivery of valsartan. Lat Am J Pharm 33(8):1237–1244Google Scholar
  24. 24.
    Hernández R, Sarafian A, López D, Mijangos C (2004) Viscoelastic properties of poly(vinyl alcohol) hydrogels and ferrogels obtained through freezing–thawing cycles. Polymer 45(16):5543–5549CrossRefGoogle Scholar
  25. 25.
    Minhas MU, Ahmad M, Ali L, Sohail M (2013) Synthesis of chemically cross-linked polyvinyl alcohol-co-poly (methacrylic acid) hydrogels by copolymerization; a potential graft-polymeric carrier for oral delivery of 5-fluorouracil. DARU J Pharm Sci 21(1):44CrossRefGoogle Scholar
  26. 26.
    Pooley SA, Rivas BL, Lillo FE, Pizarro GDC (2010) Hydrogels from acrylic acid with N, N-dimethylacrylamide: synthesis, characterization, and water absorption properties. J Chil Chem Soc 55(1):19–24CrossRefGoogle Scholar
  27. 27.
    Sanli O, Ay N, Isiklan N (2007) Release characteristics of diclofenac sodium from poly(vinyl alcohol)/sodium alginate and poly(vinyl alcohol)-grafted-poly(acrylamide)/sodium alginate blend beads. Eur J Pharm Biopharm 65:204–214CrossRefGoogle Scholar
  28. 28.
    Mandal S, Basu SK, Biswanath S (2010) Ca2+ ion cross-linked interpenetrating network matrix tablets of polyacrylamide-grafted-sodium alginate and sodium alginate for sustained release of diltiazem hydrochloride. Carbhydr Polym 82:867–873CrossRefGoogle Scholar
  29. 29.
    Yin Y, Ji X, Dong H, Ying Y, Zheng H (2008) Study of the swelling dynamics with overshooting effect of hydrogels based on sodium alginate-g-acrylic acid. Carbhydr Polym 71:682–689CrossRefGoogle Scholar
  30. 30.
    Wang W, Wang A (2010) Synthesis and swelling properties of pH-sensitive semi-IPN superabsorbent hydrogels based on sodium alginate-g-poly(sodium acrylate) and polyvinylpyrrolidone. Carbhydr Polym 80:1028–1036CrossRefGoogle Scholar
  31. 31.
    Sohail M, Ahmad M, Minhas MU, Ali L, Khalid I, Rashid H (2015) Controlled delivery of valsartan by cross-linked polymeric matrices: synthesis, in vitro and in vivo evaluation. Int J Pharm 487(1):110–119CrossRefGoogle Scholar
  32. 32.
    Khalid I, Ahmad M, Minhas MU, Sohail M (2014) Formulation and in vitro evaluation of mucoadhesive controlled release matrix tablets of flurbiprofen using response surface methodology. Braz J Pharm Sci 50(3):493–504CrossRefGoogle Scholar
  33. 33.
    Hua S, Ma H, Li X, Yang H, Wang A (2010) PH-sensitive sodium alginate/poly vinyl alcohol hydrogel beads prepared by combined Ca crosslinking and freeze–thawing cycles for controlled release of diclofenac sodium. Int J Biol Macromol 46(5):517–523CrossRefGoogle Scholar
  34. 34.
    Mansur HS, Oréfice RL, Mansur AA (2004) Characterization of poly(vinyl alcohol)/poly(ethylene glycol) hydrogels and PVA-derived hybrids by small-angle X-ray scattering and FTIR spectroscopy. Polymer 45(21):7193–7202CrossRefGoogle Scholar
  35. 35.
    Moharram M, Khafagi M (2007) Application of FTIR spectroscopy for structural characterization of ternary poly(acrylic acid)–metal–poly (vinyl pyrrolidone) complexes. J Appl Polym Sci 105(4):1888–1893CrossRefGoogle Scholar
  36. 36.
    Pereira R, Carvalho A, Vaz DC, Gil M, Mendes A, Bártolo P (2013) Development of novel alginate based hydrogel films for wound healing applications. Int J Biol Macromol 52:221–230CrossRefGoogle Scholar
  37. 37.
    Aminabhavi TM, Naik HG (2002) Synthesis of graft copolymeric membranes of poly(vinyl alcohol) and polyacrylamide for the pervaporation separation of water/acetic acid mixtures. J Appl Polym Sci 83(2):244–258CrossRefGoogle Scholar
  38. 38.
    Sand A, Yadav M, Mishra DK, Behari K (2010) Modification of alginate by grafting of N-vinyl-2-pyrrolidone and studies of physicochemical properties in terms of swelling capacity, metal-ion uptake and flocculation. Carbohydr Polym 80(4):1147–1154CrossRefGoogle Scholar
  39. 39.
    Samanta HS, Ray SK (2014) Synthesis, characterization, swelling and drug release behavior of semi-interpenetrating network hydrogels of sodium alginate and polyacrylamide. Carbohydr Polym 99:666–678CrossRefGoogle Scholar
  40. 40.
    Arndt K, Richter A, Ludwig S, Zimmermann J, Kressler J, Kuckling D, Adler H (1999) Poly(vinyl alcohol)/poly(acrylic acid) hydrogels: FT-IR spectroscopic characterization of crosslinking reaction and work at transition point. Acta Polym 50(11–12):383–390CrossRefGoogle Scholar
  41. 41.
    Mandal B, Ray SK (2013) Synthesis of interpenetrating network hydrogel from poly(acrylic acid-co-hydroxyethyl methacrylate) and sodium alginate: modeling and kinetics study for removal of synthetic dyes from water. Carbohydr Polym 98(1):257–269CrossRefGoogle Scholar
  42. 42.
    Chang C, Duan B, Zhang L (2009) Fabrication and characterization of novel macroporous cellulose–alginate hydrogels. Polymer 50(23):5467–5473CrossRefGoogle Scholar
  43. 43.
    Odian G (ed) (2004) Radical chain polymerization. In: Principles of polymerization, 4th edn, pp 198–349Google Scholar
  44. 44.
    Su W-F (2013) Principles of polymer design and synthesis. Springer, Berlin, HeidelbergCrossRefGoogle Scholar
  45. 45.
    Poorna CK, Singh A, Rathore A, Kumar A (2016) Novel cross linked guar gum-g-poly (acrylate) porous superabsorbent hydrogels: characterization and swelling behaviour in different environments. Carbohydr Polym. doi: 10.1016/j.carbpol.2016.04.077 Google Scholar
  46. 46.
    Wang Q, Zhou X, Zeng J, Wang J (2016) Water swelling properties of the electron beam irradiated PVA-g-AAc hydrogels. Nucl Instrum Method Phys Res Sect B Beam Interact Mater Atoms 368:90–95CrossRefGoogle Scholar
  47. 47.
    Murthy PK, Mohan YM, Sreeramulu J, Raju KM (2006) Semi-IPNs of starch and poly(acrylamide-co-sodium methacrylate): preparation, swelling and diffusion characteristics evaluation. React Funct Polym 66(12):1482–1493CrossRefGoogle Scholar
  48. 48.
    Hosseinzadeh H (2013) Synthesis and swelling properties of a poly(vinyl alcohol)-based superabsorbing hydrogel. CCL 2(3):153–158CrossRefGoogle Scholar
  49. 49.
    Mahdavinia G, Pourjavadi A, Hosseinzadeh H, Zohuriaan M (2004) Modified chitosan 4. Superabsorbent hydrogels from poly(acrylic acid-co-acrylamide) grafted chitosan with salt-and pH-responsiveness properties. Eur Polym J 40(7):1399–1407CrossRefGoogle Scholar
  50. 50.
    Minhas MU, Ahmad M, Anwar J, Khan S (2016) Synthesis and characterization of biodegradable hydrogels for oral delivery of 5-fluorouracil targeted to colon: screening with preliminary in vivo studies. Adv Polym Tech. doi: 10.1002/adv.21659 Google Scholar
  51. 51.
    Rashid H, Ahmad M, Minhas MU, Sohail M, Aamir MF (2015) Synthesis and characterization of poly(hydroxyethyl methacrylate-co-methacrylic acid) cross linked polymeric network for the delivery of analgesic agent. J Chem Soc Pak 37(5):999Google Scholar
  52. 52.
    Korsmeyer R, Gurny R, Doelker E, Buri P, Peppas N (1983) Mechanisms of potassium chloride release from compressed, hydrophilic, polymeric matrices: effect of entrapped air. J Pharm Sci 72(10):1189–1191CrossRefGoogle Scholar
  53. 53.
    Nadia SM, Ahmad M, Minhas MU (2017) Cross-linked β-cyclodextrin and carboxymethyl cellulose hydrogels for controlled drug delivery of acyclovir. PlosOne. doi: 10.1371/journal.pone.0172727 Google Scholar
  54. 54.
    Nadia SM, Ahmad M, Minhas MU, Murtaza G, Khalid Q (2017) Polysaccharide hydrogels for controlled release of acyclovir: development, characterization and in vitro evaluation studies. Polym Bull. doi: 10.1007/s00289-017-1952-z Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Ikrima Khalid
    • 1
  • Mahmood Ahmad
    • 1
  • Muhammad Usman Minhas
    • 1
  • Kashif Barkat
    • 1
  1. 1.Faculty of Pharmacy and Alternative MedicineThe Islamia University of BahawalpurBahawalpurPakistan

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