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Synthesis and optimization of poly (N,N-diethylacrylamide) hydrogel and evaluation of its anticancer drug doxorubicin’s release behavior

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Abstract

A macroporous temperature-responsive poly(N,N-diethylacrylamide) (PDEA) hydrogel was synthesized and optimized through free radical polymerization. The optimized hydrogel was achieved by evaluating the swelling characteristics, physical stability and mechanical strength through altering the components namely concentration of N,N-diethylacrylamide (monomer), ammonium peroxodisulfate (initiator), N,N′-methylbisacrylamide (cross-linker) and N,N,N′,N′-tetramethylethylenediamine (accelerator). The equilibrium swelling behavior was performed gravimetrically, and the PDEA hydrogel synthesized at 36 °C exhibited a maximum swelling of 18.332 g.g−1. Also, the LCST of the prepared PDEA hydrogel was found to be around 29 °C. However, the results of time-controlled swelling and deswelling kinetics indicated that hydrogels are temperature sensitive. Further, characterization of the hydrogel was performed using scanning electron microscopy, differential scanning calorimetry, thermal gravimetric analysis, and Fourier transform infrared spectroscopy. The hydrogel was assessed for its cytotoxicity in MDA-MB-231 cell line by MTT assay. The release behavior of anticancer drug doxorubicin (DOX), a hydroxyl derivative of anthracycline, was studied at above and below the LCST temperature. It was found that the DOX release from the DOX-loaded hydrogels was significantly improved when the surrounding temperature of the release media was increased near to physiological temperature. The cumulative release profile of hydrogel at different temperatures was fitted to different kinetic model equations and non-Fickian diffusion release mechanism was revealed. These results suggest that PDEA has a potential application as an intelligent drug carrier.

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References

  1. Chai Q, Jiao Y, Yu X (2017) Hydrogels for biomedical applications: their characteristics and the mechanisms behind them. Gels 3:6–21

    Article  CAS  PubMed Central  Google Scholar 

  2. Bajpai AK, Sandeep KS, Smitha B, Sanjana K (2008) Responsive polymers in controlled drug delivery. Prog Polym Sci 33:1088–1118

    Article  CAS  Google Scholar 

  3. Pinar I, Ozgur O (2017) Novel stimuli-responsive hydrogels derived from morpholine:synthesis, characterization and absorption uptake of textile azo dye. Iran Polym J 26:391–404

    Article  CAS  Google Scholar 

  4. Kamath K, Park K (1993) Biodegradable hydrogels in drug delivery. Adv Drug Deliv Rev 11:59–84

    Article  CAS  Google Scholar 

  5. Park K, Shalaby WSW, Park H (1993) Biodegradable hydrogel for drug delivery. Technomic Publishing Co., Inc. Lancaster,

    Google Scholar 

  6. Liu F, Tao GL, Zhuo RX (1993) Synthesis of thermal phase-separating reactive polymers and their applications in immobilized enzymes. Polym J 25:561–567

    Article  CAS  Google Scholar 

  7. Kim JJ, Park K (1999) Smart hydrogels for bioseparation. Bioseparation 7:177–184

    Article  CAS  Google Scholar 

  8. Chen JK, Chang CJ (2014) Fabrications and applications of stimulus-responsive polymer films and patterns on surfaces: a review. Materials 7:805–875

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hoffman AS (2012) Hydrogels for biomedical applications. Adv Drug Deliv Rev 64:18–23

    Article  Google Scholar 

  10. Sosnik A, Seremeta KP (2017) Polymeric hydrogels as technology platform for drug delivery applications. Gels 3:25–47

    Article  CAS  PubMed Central  Google Scholar 

  11. Caló E, Khutoryanskiy VV (2015) Biomedical applications of hydrogels: a review of patents and commercial products. Eur Polym J 65:252–267

    Article  CAS  Google Scholar 

  12. Ullah F, Othman MB, Javed F, Ahmad Z, MdAkil H (2015) Classification, processing and application of hydrogels: a review. Mater Sci Eng C 57:414–433

    Article  CAS  Google Scholar 

  13. Kondiah PJ, Choonara YE, Kondiah PPD, Marimuthu T, Kumar P, du Toit LC, Pillay V (2016) A review of injectable polymeric hydrogel systems for application in bone tissue engineering. Molecules 21:1580–1611

    Article  CAS  PubMed Central  Google Scholar 

  14. Bahram M, Mohseni N, Moghtader M (2016) In: Majee SB (ed) An introduction to hydrogels and some recent applications. IntechOpen London

    Chapter  Google Scholar 

  15. Strandman S, Zhu XX (2015) Thermo-responsive block copolymers with multiple phasetransition temperatures in aqueous solutions. Prog Polym Sci 42:154–176

    Article  CAS  Google Scholar 

  16. Xiao XC (2007) Effect of the initiator on thermosensitive rate of poly(N-isopropylacrylamide) hydrogels. Express Polym Lett 1:232–235

    Article  CAS  Google Scholar 

  17. Karimi M, Sahandi PZ, Ghasemi A, Amiri M, Bahrami M (2016) Temperature-responsive smart nanocarriers for delivery of therapeutic agents: applications and recent advances. ACS Appl Mater Interfaces 8:21107–21133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Patil JS, Gurav PB, Mandave SV, Jadhav SM, Kulkarni RG (2014) Hydrogel system, a ‘smart’ and ‘intelligent’ drug delivery device: a systematic and concise review. Ind J Nov Drug Deliv 6:93–105

    Google Scholar 

  19. Rizwan M, Yahya R, Hassan A, Yar M, Azzahari AD, Selvanathan V, Sonsudin F, Abouloula CN (2017) pH sensitive hydrogels in drug delivery: brief history, properties, swelling, and release mechanism, material selection and applications. Polymers 9:137–174

    Article  CAS  PubMed Central  Google Scholar 

  20. Simões S, Figueiras A, Veiga F (2012) Modular hydrogels for drug delivery. J Biomater Nanobiotechnol 3:185–199

    Article  CAS  Google Scholar 

  21. Wang L, Li B, Xu F, Xu Z, Wei D, Feng Y, Wang Y, Jia D, Zhou Y (2017) UV-crosslinkable and thermo-responsive chitosan hybrid hydrogel for NIR-triggered localized on-demand drug delivery. Carbohydr Polym 174:904–914

    Article  CAS  PubMed  Google Scholar 

  22. Wei W, Qi X, Li J, Zuo G, Sheng W, Zhang J, Dong W (2016) Smart macroporous salecan/poly (N,N-diethylacrylamide) semi-IPN hydrogel for anti-inflammatory drug delivery. ACS Biomater Sci Eng 2:1386–1394

    Article  CAS  Google Scholar 

  23. Işıklan N, Kazan H (2018) Thermoresponsive and biocompatible poly(vinyl alcohol)-graft poly(N,N-diethylacrylamide) copolymer: microwave-assisted synthesis, characterization, and swelling behavior. J Appl Polym Sci 135:45969

    Article  CAS  Google Scholar 

  24. Işıklan N, Ş Tokmak (2018) Microwave based synthesis and spectral characterization of thermo-sensitive poly(N,N-diethylacrylamide) grafted pectin copolymer. Int J Biol Macromol 113:669–680

    Article  CAS  PubMed  Google Scholar 

  25. Ngadaonye JI, Geever LM, Killion J, Higginbotham CL (2013) Development of novel chitosan-poly(N,N-diethylacrylamide) IPN films for potential wound dressing and biomedical applications. J Polym Res 20:161–174

    Article  CAS  Google Scholar 

  26. Ngadaonye JI, Geever LM, McEvoy KE, Killion J, Brady DB, Higginbotham CL (2014) Evaluation of novel antibiotic-eluting thermoresponsive chitosan-PDEAAm based wound dressings. Int J Polym Mater Po 63:873–883

    Article  CAS  Google Scholar 

  27. Li H, Wu R, Zhu J, Guo P, Ren W, Xu S, Wang J (2015) pH/temperature double responsive behaviors and mechanical strength of laponite-crosslinked poly(DEA-co-DMAEMA) nanocomposite hydrogels. J Polym Sci B 53:876–884

    Article  CAS  Google Scholar 

  28. Kohsaka Y, Tanimoto Y (2016) Synthesis of thermo-responsive polymer via radical (co)polymerization of N,N-dimethyl-α-(hydroxymethyl)acrylamide with N,N-diethyl acrylamide. Polymers 8:374–381

    Article  CAS  PubMed Central  Google Scholar 

  29. Hanyková L, Spěváček J, Radecki M, Zhigunov A, Kouřilová H, Sedláková Z (2016) Phase transition in hydrogels of thermoresponsive semi-interpenetrating and interpenetrating networks of poly(N,N-diethylacrylamide) and polyacrylamide. Eur Polym J 85:1–13

    Article  CAS  Google Scholar 

  30. Maheswari B, Babu PEJ, Agarwal M (2014) Role of N-vinyl-2-pyrrolidinone on the thermoresponsive behavior of PNIPAm hydrogel and its release kinetics using dye and vitamin-B12 as a model drug. J Biomater Sci Polym Ed 25:269–286

    Article  CAS  PubMed  Google Scholar 

  31. Qi X, Wei W, Li J, Liu Y, Hu X, Zhang J, Bi L, Dong W (2015) Fabrication and characterization of a novel anticancer drug delivery system: salecan/poly(methacrylic acid) semi-interpenetrating polymer network hydrogel. ACS Biomater Sci Eng 1:1287–1299

    Article  CAS  Google Scholar 

  32. Dash S, Murthy PN, Nath L, Chowdhury P (2010) Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm 67:217–223

    CAS  Google Scholar 

  33. Siegel RA, Rathbone MJ (2012) In: Siepmann J, Siegel RA, Rathbone MJ (eds) Fundamentals and applications of controlled release drug delivery. Springer, New York

    Google Scholar 

  34. Šponarov ÁD, Horák D (2008) Poly (N,N-diethyl acrylamide) microspheres by dispersion polymerization. J Poly Sci Part A Pol Chem 46:6263–6271

    Article  CAS  Google Scholar 

  35. Flory PJ (1953) Principles of polymer chemistry. Cornell University Press, New York

    Google Scholar 

  36. Barron V, Killion JA, Pilkington L, Burke G, Geever LM, Lyons JG, McCullagh E, Higginbotham CL (2016) Development of chemically cross-linked hydrophilic–hydrophobic hydrogels for drug delivery applications. Eur Polym J 75:25–35

    Article  CAS  Google Scholar 

  37. Wang WB, Wang AQ (2010) Preparation, swelling and water-retention properties of cross-linked superabsorbent hydrogels based on guar gum. Adv Mater Res 96:177–182

    Article  CAS  Google Scholar 

  38. Zhang N, Liu M, Shen Y, Chen J, Dai L, Gao C (2011) Preparation, properties, and drug release of thermo- and pH-sensitive poly(2-dimethylamino)ethyl methacrylate)/poly(N,N-diethylacrylamide) semi-IPN hydrogels. J Mater Sci 46:1523–1534

    Article  CAS  Google Scholar 

  39. Yin L, Fei L, Cui F, Tang C, Yin C (2007) Superporous hydrogels containing poly(acrylic acid-co-acrylamide)/O-carboxymethyl chitosan interpenetrating polymer networks. Biomaterials 28:1258–1266

    Article  CAS  PubMed  Google Scholar 

  40. Wang ZC, Xu XD, Chen CS, Wang GR, Wang B, Zhang XZ, Zhuo RX (2008) Study of novel hydrogels based on thermosensitive PNIPAAm with pH-sensitive PDMAEMA grafts. Colloids Surf B 67:245–252

    Article  CAS  Google Scholar 

  41. Babu PEJ, Kumar RS, Maheswari B (2011) Synthesis and characterization of temperature sensitive P-NIPAM macro/micro hydrogels. Colloids Surf A 384:466–472

    Article  CAS  Google Scholar 

  42. Chen J, Liu M, Chen W, Zhang N, Zhu S, Zhang S, Xiong Y (2011) Synthesis, swelling and drug-release behavior of a poly(N,N-diethyl acrylamide-co-(2-dimethylamino) ethyl methacrylate) hydrogel. J Biomater Sci Polym Ed 22:1049–1068

    Article  CAS  PubMed  Google Scholar 

  43. Chen J, Liu M, Liu H, Ma L, Gao C, Zhu S, Zhang S (2010) Synthesis and properties of thermo- and pH-sensitive poly(diallyldimethylammonium chloride)/poly(N,N-diethylacrylamide) semi-IPN hydrogel. Chem Eng J 159:247–256

    Article  CAS  Google Scholar 

  44. Ngadaonye JI, Geever LM, Cloonan MO, Higginbotham CL (2012) Photopolymerised thermo-responsive poly(N,N-diethyl acrylamide)-based copolymer hydrogels for potential drug delivery applications. J Polym Res 19:9822–9837

    Article  CAS  Google Scholar 

  45. Qi X, Wei W, Li J, Zuo G, Hu X, Zhang J, Dong W (2016) Development of novel hydrogels based on Salecan and poly(N-isopropylacrylamide-co-methacrylic acid) for controlled doxorubicin release. RSC Adv 6:69869–69881

    Article  CAS  Google Scholar 

  46. Chen J, Liu M, Liu H, Ma L (2009) Synthesis, swelling and drug release behavior of poly(N,N-diethylacrylamide-co-N-hydroxymethyl acrylamide) hydrogel. Mater Sci Eng C 29:2116–2123

    Article  CAS  Google Scholar 

  47. Akın A, Işıklan N (2016) Microwave-assisted synthesis and characterization of sodium alginate-graft-poly (N,N′-dimethylacrylamide). Int J Biol Macromol 82:530–540

    Article  CAS  PubMed  Google Scholar 

  48. Brazel CS, Peppas NA (1999) Mechanisms of solute and drug transport in relaxing, swellablehydrophilic glassy polymers. Polymer 40:3383–3398

    Article  CAS  Google Scholar 

  49. Hoffman AS (2002) Hydrogels for biomedical applications. Adv Drug Deliv Rev 54:3–12

    Article  CAS  PubMed  Google Scholar 

  50. Zhao L, Zhang X, Liu X, Li J, Luan Y (2017) pH-responsive poly(ethylene glycol)-poly(ɛ-caprolactone)-poly(glutamic acid) polymersome as an efficient doxorubicin carrier for cancer therapy. Polym Int 66:1579–1586

    Article  CAS  Google Scholar 

  51. Fariba G, Ebrahim VF (2009) Hydrogels in controlled drug delivery systems. Iran Polym J 18:63–88

    Google Scholar 

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Havanur, S., Farheenand, V. & JagadeeshBabu, P.E. Synthesis and optimization of poly (N,N-diethylacrylamide) hydrogel and evaluation of its anticancer drug doxorubicin’s release behavior. Iran Polym J 28, 99–112 (2019). https://doi.org/10.1007/s13726-018-0680-z

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