Skip to main content
Log in

Graphene oxide/poly(N-isopropyl acrylamide)/sodium alginate-based dual responsive composite beads for controlled release characteristics of chemotherapeutic agent

  • Original Article
  • Published:
Iranian Polymer Journal Aims and scope Submit manuscript

Abstract

In this work, graphene oxide (GO)-incorporated composite beads were developed from poly(N-isopropyl acrylamide)/sodium alginate (PNIPAM/NaAlg) using ionotropic gelation technique. The interaction between GO and PNIPAM/NaAlg with Ca2+ ions as a cross-linker was investigated by Fourier transform spectroscopy. X-Ray diffraction pattern showed that the GO was distributed uniformly in the PNIPAM/NaAlg with Ca2+ ions while scanning electron micrograph technique revealed that composite beads were formed in spherical shape. The controlled release characteristics of composite beads were studied using 5-fluorouracil (5-FU) as anti-cancer model drug. The encapsulation efficiencies were found to be between 90 and 92% in all formulations. Furthermore, the equilibrium swelling ratio (%) and in vitro release studies of the beads were carried out in two different pH values of 1.2 and 7.4 and at different temperature conditions of 25 and 37 °C. The obtained results showed that the swelling ratio decreased with an increase in GO concentration. In vitro release studies performed in response to both pH and temperature and they proved that the 5-FU drug was released from composite beads over 32 h without burst release. Cytotoxicity results showed pristine composite beads are good cytocompatible. In addition, the cytotoxicity of 5-FU was found to be improved when incorporated with composite beads than pure 5-FU. It is therefore concluded that the developed composite beads have dual response and can be used as controlling released carriers in cancer drug delivery applications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  1. Shilpa A, Agrawal SS, Ray AR (2003) Controlled delivery of drugs from alginate matrix. J Macromol Sci Part C-Polym Rev 43:187–221

    Article  Google Scholar 

  2. Becker TA, Kipke DR, Brandon T (2001) Calcium alginate gel: a biocompatible and mechanically stable polymer for endovascular embolization. J Biomed Mater Res 54:76–86

    Article  CAS  Google Scholar 

  3. Martins S, Sarmento B, Souto EB, Ferreira DC (2007) Insulin-loaded alginate microspheres for oral delivery-effect of polysaccharide reinforcement on physicochemical properties and release profile. Carbohydr Polym 69:725–731

    Article  CAS  Google Scholar 

  4. Rowley JA, Madlambayan G, Mooney DJ (1999) Alginate hydrogels as synthetic extracellular matrix materials. Biomaterials 20:45–53

    Article  CAS  Google Scholar 

  5. Ferreira Almeida P, Almeida AJ (2004) Cross-linked alginate-gelatin beads: a new matrix for controlled release of pindolol. J Control Release 97:431–439

    Article  CAS  Google Scholar 

  6. Nochos A, Douroumis D, Bouropoulos N (2008) In vitro release of bovine serum albumin from alginate/HPMC hydrogel beads. Carbohydr Polym 74:451–457

    Article  CAS  Google Scholar 

  7. Pongjanyakul T, Rongthong T (2010) Enhanced entrapment efficiency and modulated drug release of alginate beads loaded with drug-clay intercalated complexes as micro-reservoirs. Carbohydr Polym 81:409–419

    Article  CAS  Google Scholar 

  8. Shiraishi S, Imai T, Iwaoka D, Otagiri M (1991) Improvement of absorption rate of indomethacin and reduction of stomach irritation by alginate dispersions. J Pharm Pharmacol 43:615–620

    Article  CAS  Google Scholar 

  9. Kim CK, Lee EJ (1992) The controlled release of blue dextran from alginate beads. Int J Pharm 79:11–19

    Article  CAS  Google Scholar 

  10. Yotsuyanagi T, Ohkubo T, Ohhashi T, Ikeda K (1987) Calcium-induced gelation of alginic acid and pH-sensitive reswelling of dried gels. Chem Pharm Bull 35:1555–1563

    Article  CAS  Google Scholar 

  11. Sugawara S, Imai T, Otagiri M (1994) The controlled release of prednisolone using alginate gel. Pharm Res 11:272–277

    Article  CAS  Google Scholar 

  12. Mallikarjuna Reddy K, Ramesh Babu V, Krishna Rao KSV, Subha MCS, Chowdoji Rao K, Sairam M, Aminabhavi TM (2008) Temperature sensitive semi-IPN microspheres from sodium alginate and N-isopropyl acrylamide for controlled release of 5-fluorouracil. J Appl Polym Sci 107:2820–2829

    Article  Google Scholar 

  13. Krishna Rao KSV, Subha MCS, Vijaya Kumar Naidu B, Sairam M, Mallikarjuna NN, Aminabhavi TM (2006) Controlled release of diclofenac sodium and ibuprofen through beads of sodium alginate and hydroxyethyl cellulose blends. J Appl Polym Sci 2:5708–5718

    Article  Google Scholar 

  14. Madhusudana Rao K, Krishna Rao KSV, Sudhakar P, Chowdoji Rao K, Subha MCS (2013) Synthesis and characterization of biodegradable poly(vinyl caprolactam) grafted on to sodium alginate and its microgels for controlled release studies of an anticancer drug. J Appl Pharm Sci 3:61–69

    Google Scholar 

  15. Zhao F, Li H, Wang X, Wu L, Hou T, Guan J, Jiang Y, Xu H, Mu X (2015) CRGO/alginate microbeads: an enzyme immobilization system and its potential application for a continuous enzymatic reaction. J Mater Chem B 3:9315–9322

    Article  CAS  Google Scholar 

  16. Ai Q, Yang D, Zhu Y, Jiang Z (2013) Fabrication of boehmite/alginate hybrid beads for efficient enzyme immobilization. Ind Eng Chem Res 52:14898–14905

    Article  CAS  Google Scholar 

  17. Karkeh-abadi F, Saber-Samandari S, Saber-Samandari S (2016) The impact of functionalized CNT in the network of sodium alginate-based nanocomposite beads on the removal of Co(II) ions from aqueous solutions. J Hazard Mater 312:224–233

    Article  CAS  Google Scholar 

  18. Pan Y, Bao H, Sahoo NG, Wu T, Li L (2011) Water-soluble poly(N-isopropyl acrylamide)-graphene sheets synthesized via click chemistry for drug delivery. Adv Funct Mater 21:2754–2763

    Article  CAS  Google Scholar 

  19. Wang J, Liu C, Shuai Y, Cui X, Nie L (2014) Controlled release of anticancer drug using graphene oxide as a drug-binding effector in konjac glucomannan/sodium alginate hydrogels. Colloid Surf B: Biointerf 113:223–229

    Article  CAS  Google Scholar 

  20. Seo HI, Cheon YA, Chung BG (2016) Graphene and thermoresponsive polymeric nanocomposites for therapeutic applications. Biomed Eng Lett 6:10–15

    Article  Google Scholar 

  21. Sun X, Liu Z, Welsher K, Robinson JT, Goodwin A, Zaric S, Dai H (2008) Nano-graphene oxide for cellular imaging and drug delivery. Nano Res 1:203–212

    Article  CAS  Google Scholar 

  22. Zhang B, Yan Y, Shen Q, Ma D, Huang L, Cai X, Tan S (2017) A colon targeted drug delivery system based on alginate modificated graphene oxide for colorectal liver metastasis. Mater Sci Eng C Mater Biol Appl 79:185–190

    Article  CAS  Google Scholar 

  23. Tian B, Wang C, Zhang S, Feng L, Liu Z (2011) Photothermally enhanced photodynamic therapy delivered by nano-graphene oxide. ACS Nano 5:7000–7009

    Article  CAS  Google Scholar 

  24. Lee S-K, Hyun Kim H, Shim BS (2013) Graphene: an emerging material for biological tissue engineering. Carbon Lett 14:63–75

    Article  Google Scholar 

  25. Wan Y, Chen X, Xiong G, Guo R, Luo H (2014) Synthesis and characterization of three-dimensional porous graphene oxide/sodium alginate scaffolds with enhanced mechanical properties. Mater Express 4:429–434

    Article  CAS  Google Scholar 

  26. Aliabadi M, Shagholani H, Yunessnia A (2017) Synthesis of a novel biocompatible nanocomposite of graphene oxide and magnetic nanoparticles for drug delivery. Int J Biol Macromol 98:287–291

    Article  CAS  Google Scholar 

  27. Qixia P, Yao L, Gareth RW, Lei T, Huihui Y, Heyu L, Limin Z (2016) Lactobionic acid and carboxymethyl chitosan functionalized graphene oxide nanocomposites as targeted anticancer drug delivery systems. Carbohydr Polym 151:812–820

    Article  Google Scholar 

  28. Xie RH, Hui Ren PG, Ren F, Ren LZ, Sun ZF (2016) Preparation and properties of graphene oxide-regenerated cellulose/polyvinyl alcohol hydrogel with pH-sensitive behavior. Carbohydr Polym 138:222–228

    Article  CAS  Google Scholar 

  29. Cayre OJ, Chagneuxb N, Biggs S (2011) Stimulus responsive core-shell nanoparticles: synthesis and applications of polymer based aqueous systems. Soft Matter 7:2211–2234

    Article  CAS  Google Scholar 

  30. Zhu XL, Liu YX, Huang JY, Li GX (2010) A pH-responsive gate fabricated with nano-channels and nano-particles. Chem Eur J 16:1441–1444

    Article  CAS  Google Scholar 

  31. Choi HS, Huh KM, Ooya T, Yui N (2003) pH-and thermosensitive supramolecular assembling system: rapidly responsive properties of β-cyclodextrin-conjugated poly(ε-lysine). J Am Chem Soc 125:6350–6351

    Article  CAS  Google Scholar 

  32. Chang BS, Sha XY, Guo J, Jiao YF, Wang CC, Yang WL (2011) Thermo and pH dual responsive, polymer shell coated, magnetic mesoporous silica nanoparticles for controlled drug release. J Mater Chem 21:9239–9247

    Article  CAS  Google Scholar 

  33. Zhang LY, Guo R, Yang M, Jiang XQ, Liu BR (2007) Thermo and pH dual-responsive nanoparticles for anti-cancer drug delivery. Adv Mater 19:2988–2992

    Article  CAS  Google Scholar 

  34. Garbern JC, Hoffman AS, Stayton PS (2010) Injectable pH- and temperature- responsive poly(N-isopropylacrylamide-co-propyl acrylic acid) copolymers for delivery of angiogenic growth factors. Biomacromolecules 11:1833–1839

    Article  CAS  Google Scholar 

  35. Wei C, Xuemin L, Kun C, Lvye N, Yen W, Qinghua L (2012) Dual responsive controlled release drug delivery based on ionically assembled nanoparticles. Langmuir 28:9413–9420

    Article  Google Scholar 

  36. Amanda Higginbotham L, Jay Lomeda R, Alexander Morgan B, James Tour M (2009) Graphite oxide flame-retardant polymer nanocomposites. Appl Mater Interf 1:2256–2261

    Article  Google Scholar 

  37. Hummers WS (1958) Preparation of graphitic oxide. J Am Chem Soc 80:1339

    Article  CAS  Google Scholar 

  38. Mallikarjuna B, Madhusudhana Rao K, Prasad CV, Chowdoji Rao K, Krishna Rao KSV, Subha MCS (2011) Synthesis, characterization and use of poly(N-isopropyl acrylamide-co-N-vinyl caprolactam) cross-linked thermo- responsive microspheres for control release of ciprofloxacin hydrochloride drug. J Appl Pharm Sci 1:171–177

    Google Scholar 

  39. Fundueanu G, Constantin M, Bortolotti F, Ascenzi P, Cortesi R, Menegatti E (2005) Preparation and characterisation of thermoresponsive poly[(N-isopropyl acrylamide-co-acrylamide-co-(hydroxyethyl acrylate)] microspheres as a matrix for the pulsed release of drugs. Macromol Biosci 5:955–964

    Article  CAS  Google Scholar 

  40. Kim Y, Babu VR, Rao KSV, Lim JM, Thangadurai TD, Lee Y-L (2014) Stimuli-sensitive poly(NIPA-co-APA) hydrogels for the controlled release of keterolac tromethamine. J Korean Chem Soc 58:92–99

    Article  CAS  Google Scholar 

  41. Ritger PL, Peppas NAA (1987) Simple equation for description of solute release II. Fickian and anomalous release from swellable devices. J Control Release 5:37–42

    Article  CAS  Google Scholar 

  42. Takara K, Sakaeda T, Yagami T, Kobayashi H, Ohmoto N, Horinouchi M, Nishiguchi K, Okumura K (2002) Cytotoxic effects of 27 anticancer drugs in HeLa and MDR1-overexpressing derivative cell lines. Biol Pharm Bull 25:771–778

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The first author is highly grateful to the University of South Africa for Postdoctoral research fellowship.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kuncham Sudhakar.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sudhakar, K., Moloi, S.J. & Rao, K.M. Graphene oxide/poly(N-isopropyl acrylamide)/sodium alginate-based dual responsive composite beads for controlled release characteristics of chemotherapeutic agent. Iran Polym J 26, 521–530 (2017). https://doi.org/10.1007/s13726-017-0543-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13726-017-0543-z

Keywords

Navigation