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Synthesis of stimuli-responsive poly(ethylene glycol) diacrylate/methacrylic acid-based nanogels and their application as drug delivery vehicle

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Abstract

A series of poly(ethylene glycol) diacrylate/methacrylic acid (PEGDA/MAA)-based nanogels showing multiresponsiveness toward temperature, salt concentration, and pH value were synthesized by aqueous precipitation polymerization. The effect of monomer loading amount, cross-linking degree, and cross-linker type on synthesis of hydrogels was investigated, and so were the influences of MAA content in the feed of synthesis of hydrogel, pH value, and NaCl concentration on the thermosensitivity of hydrogels. The lower critical solution temperature (LCST) of poly(PEGDA/MAA) hydrogels decreased with an increase of MAA content or NaCl concentration and a decrease of pH value. One of the resultant hydrogels (PEGDA575/MAA, 40/60 mol/mol) displayed a distinct LCST of 35 °C under a gastric liquid-like condition (pH 1.0, 150 mM NaCl). Such hydrogel showed a good potential in controlling the release of 5-fluorouracil (5-FU), an anticancer agents, under the above gastric liquid-like condition and also an intestinal liquid-like one.

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References

  1. Wilson AN, Anthony GE (2013) Bioresponsive hydrogels. Adv Healthcare Mater 2:520–532

    Article  CAS  Google Scholar 

  2. Pelton R (2000) Temperature-sensitive aqueous microgels. Adv Colloid Interf Sci 85:1–33

    Article  CAS  Google Scholar 

  3. Chen ZY, Xu L, Liang Y, Zhao MP (2010) pH-sensitive water-soluble nanospheric imprinted hydrogels prepared as horseradish peroxidase mimetic enzymes. Adv Mater 22:1488–1492

    Article  CAS  Google Scholar 

  4. Meng FH, Zhong ZY, Jan F (2009) Stimuli-responsive polymersomes for programmed drug delivery. Biomaterials 10(2):198–209

    Google Scholar 

  5. Gawel K, Barriet D, Sletmoen M, Stokke BT (2010) Responsive hydrogels for label-free signal transduction within biosensors. Sensors 10:4381–4409

    Article  CAS  Google Scholar 

  6. Ottenbrite RM, Park K, Okano T (2010) Biomedical applications of hydrogels handbook. In: Yoshida Y, Okano T (eds) Stimuli-Responsive Hydrogels and Their Application to Functional Materials, 3rd edn. Springer Science, New York, pp 19–22

    Google Scholar 

  7. Mackenzie KJ, Francis MB (2012) Recyclable thermoresponsive polymer cellulase bioconjugates for biomass depolymerization. J Am Chem Soc 135:293–300

    Article  Google Scholar 

  8. Yang XY, Chen LT, Huang B, Bai F, Yang XL (2009) Synthesis of pH-sensitive hollow polymer microspheres and their application as drug carriers. Polymer 50:3556–3563

    Article  CAS  Google Scholar 

  9. Kaewsaiha P, Matsumoto K, Matsuoka H (2007) Salt effect on the nanostructure of strong polyelectrolyte brushes in amphiphilic diblock copolymer monolayers on the water surface. Langmuir 23:7065–7071

    Article  CAS  Google Scholar 

  10. Yan Q, Yuan JY, Cai ZN, Xin Y, Kang Y, Yin YW (2010) Voltage-responsive vesicles based on orthogonal assembly of two homopolymers. J Am Chem Soc 132:9268–9270

    Article  CAS  Google Scholar 

  11. Xu SF, Lu HZ, Zheng XW, Chen LX (2013) Stimuli-responsive molecularly imprinted polymers: versatile functional materials. J Mater Chem C 1:4406–4422

    Article  CAS  Google Scholar 

  12. Wagner V, Dullaart A, Bock AK, Zweck A (2006) The emerging nanomedicine landscape Biotechnol. Nat Biotechnol 24:1211–1217

    Article  CAS  Google Scholar 

  13. Kabanov AV, Vinogradov SV (2009) Nanogels as pharmaceutical carriers: finite networks of infinite capabilities. Angew Chem Int Ed 48:5418–5429

    Article  CAS  Google Scholar 

  14. Zha LS, Hu JH, Wang CC, Fu SK, Luo MF (2002) The effect of electrolyte on the colloidal properties of poly(N-isopropylacrylamide-co dimethylaminoethylmethacrylate) microgel latexes. Colloid Polym Sci 280:1116–1121

    Article  CAS  Google Scholar 

  15. Kratz K, Hellweg T, Eimer W (2000) Influence of charge density on the swelling of colloidal poly(N-isopropylacrylamide-co-acrylic acid) microgels. Colloids Surf A 170:137–149

    Article  CAS  Google Scholar 

  16. Dai WF, Zhang Y, Du ZZ, Ru ML, Lang MD (2010) The pH-induced thermosensitive poly (NIPAAm-co-AAc-co-HEMA)-g-PCL micelles used as a drug carrier. J Mater Sci Mater Med 21:1881–1890

    Article  CAS  Google Scholar 

  17. Tomić SLJ, Mićić MM, Filipović JM, Suljovrujić EH (2010) Synthesis, characterization and controlled release of cephalexin drug from smart poly(2-hydroxyethyl methacrylate/poly(alkylene glycol) (meth) acrylates hydrogels. Chem Eng J 160:801–809

    Article  Google Scholar 

  18. Zhang Y, Chan HF, Leong KW (2013) Advanced materials and processing for drug delivery: The past and the future. Adv Drug Deliv Rev 65:104–120

    Article  CAS  Google Scholar 

  19. Liao Q, Shao QL, Wang HY, Qiu G, Lu XH (2012) Hydroxypropylcellulose templated synthesis of surfactant-free poly(acrylic acid) nanogels in aqueous media. Carbohydr Polym 87:2648–2654

    Article  CAS  Google Scholar 

  20. Lai HJ, Chen GT, Wu PY, Li ZC (2012) Thermoresponsive behavior of an LCST-type polymer based on a pyrrolidone structure in aqueous solution. Soft Matter 8:2662–2670

    Article  CAS  Google Scholar 

  21. Zhang HB, Wang L, Song L, Niu GG, Cao H, Wang GJ, Yang H, Zhu SQ (2011) Controllable properties and microstructure of hydrogels based on crosslinked poly(ethylene glycol) diacrylates with different molecular weights. J Appl Polym Sci 121:531–540

    Article  CAS  Google Scholar 

  22. Patel PN, Smith CK, Patrick CW (2005) Rheological and recovery properties of poly(ethylene glycol) diacrylate hydrogels and human adipose tissue. J Biomed Mater Res 73(3):313–319

    Article  Google Scholar 

  23. Saeki S, Kuwahara N, Nakata M, Kaneko M (1976) Upper and lower critical solution temperatures in poly (ethylene glycol) solutions. Polymer 17:685–689

    Article  CAS  Google Scholar 

  24. Lutz JF, Akdemir Ö, Hoth A (2006) Point by point comparison of two thermosensitive polymers exhibiting a similar LCST: is the age of poly (NIPAM) over? J Am Chem Soc 128:13046–13047

    Article  CAS  Google Scholar 

  25. Mori H, Tsukamoto M (2011) RAFT polymerization of diacrylate derivatives having different spacers in dilute conditions. Polymer 52:635–645

    Article  CAS  Google Scholar 

  26. Yoshitomi T, Miyamoto D, Nagasaki Y (2009) Design of core-shell-type nanoparticles carrying stable radicals in the core. Biomacromolecules 10:596–601

    Article  CAS  Google Scholar 

  27. Oishi M, Tamura A, Nakamura T, Nagasaki Y (2009) A smart nanoprobe based on fluorescence-quenching PEGylated nanogels containing gold nanoparticles for monitoring the response to cancer therapy. Adv Funct Mater 19:827–834

    Article  CAS  Google Scholar 

  28. Lee AS, Gast AP, Bütün V, Armes SP (1999) Dendrimer-based contrast agents for molecular imaging. Macromolecules 32:4302–4310

    Article  CAS  Google Scholar 

  29. Es-Haghi H, Bouhendi H, Bagheri MG, Zohurian-Mehr MJ, Kabiri K (2012) Rheological properties of microgel prepared with long-chain crosslinkers by a precipitation polymerization method. J Macromol Sci Phys 51:880–896

    Article  CAS  Google Scholar 

  30. Lally S, Liu RX, Supasuteekul C, Saunders BR, Freemont T (2011) Using osmotic deswelling of microgel particles to control the mechanical properties of pH-responsive hydrogel composites. J Mater Chem 21:17719–17728

    Article  CAS  Google Scholar 

  31. Kumar A, Lahiri SS, Punyani S, Singh H (2008) Synthesis and characterization of pH sensitive poly(PEGDMA-MAA) copolymeric microparticles for oral insulin delivery. J Appl Polym Sci 107:863–871

    Article  CAS  Google Scholar 

  32. Tomar LK, Tyagi C, Lahiri SS, Singh H (2011) Poly(PEGDMA-MAA) copolymeric micro and nanoparticles for oral insulin delivery. Polym Adv Technol 22:1760–1767

    Article  CAS  Google Scholar 

  33. Muzzalupo R, Tavano L, Cassano R, Trombino S, Cilea A, Picci N (2010) Colon-specific devices based on methacrylic functionalized Tween monomer networks: Swelling studies and in vitro drug release. Eur Polym J 46:209–216

    Article  CAS  Google Scholar 

  34. Chen WL, Shen YY, Rong HJ, Lei L, Guo SR (2012) Development and application of a validated gradient elution HPLC method for simultaneous determination of 5-fluorouracil and paclitaxel in dissolution samples of 5-fluorouracil/paclitaxel-co-eluting stents. J Pharm Biomed Anal 59:179–183

    Article  CAS  Google Scholar 

  35. Singh B, Chauhan N (2008) Preliminary evaluation of molecular imprinting of 5-fluorouracil within hydrogels for use as drug delivery systems. Acta Biomater 4:1244–1254

    Article  CAS  Google Scholar 

  36. Li GY, Guo L, Wen QW, Zhang T (2013) Thermo- and pH-sensitive ionic-crosslinked hollow spheres from chitosan-based graft copolymer for 5-fluorouracil release. Int J Biol Macromol 55:69–74

    Article  CAS  Google Scholar 

  37. Puoci F, Iemma F, Cirillo G, Picci N, Matricardi P, Alhaique F (2007) Molecularly imprinted polymers for 5-fluorouracil release in biological fluids. Molecules 12:805–814

    Article  CAS  Google Scholar 

  38. Yang M, Liu C, Li ZY, Gao G, Liu FQ (2010) Temperature-responsive properties of poly(acrylic acid-co-acrylamide) hydrophobic association hydrogels with high mechanical strength. Macromolecules 43:10645–10651

    Article  CAS  Google Scholar 

  39. Knipe JM, Chen F, Peppas NA (2014) Multiresponsive polyanionic microgels with inverse pH responsive behavior by encapsulation of polycationic nanogels. J Appl Polym Sci. doi:10.1002/APP.40098

    Google Scholar 

  40. Wang CY, Javadi A, Ghaffar M, Gong SQ (2010) A pH-sensitive molecularly imprinted nanospheres/hydrogel composite as a coating for implantable biosensors. Biomaterials 31:4944–4951

    Article  CAS  Google Scholar 

  41. Wu YL, Chen W, Meng FH, Wang ZJ, Cheng R, Deng C, Liu HY, Zhong ZY (2012) Core-crosslinked pH-sensitive degradable micelles: a promising approach to resolve the extracellular stability versus intracellular drug release dilemma. J Control Release 164:338–345

    Article  CAS  Google Scholar 

  42. Zadražil A, Štĕpánek F (2010) Investigation of thermo-responsive optical properties of a composite hydrogel. Colloids Surf A 372:115–119

    Article  Google Scholar 

  43. Park TG, Hoffman AS (1993) Sodium chloride-Induced phase transition in nonionic poly(N-isopropylacrylamide) gel. Macromolecules 26:5045–5048

    Article  CAS  Google Scholar 

  44. Yin XC, Stöver HDH (2002) Thermosensitive and pH-sensitive polymers based on maleic anhydride copolymers. Macromolecules 35:10178–10181

    Article  CAS  Google Scholar 

  45. Fournier E, Passirani C, Colin N, Breton P, Sagodira S, Benoit JP (2004) Development of novel 5-FU-loaded poly (methylidene malonate 2.1.2)-based microspheres for the treatment of brain cancers. Eur J Pharm Biopharm 57:189–197

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank startup funds from University of Jinan, National College Student Innovation Training Program (No. 20131427023) and the National Nature Science Foundation of China (No. 21274054) for financial support.

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Correspondence to Zhiyong Chen.

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Cao, H., Wang, Q., Li, M. et al. Synthesis of stimuli-responsive poly(ethylene glycol) diacrylate/methacrylic acid-based nanogels and their application as drug delivery vehicle. Colloid Polym Sci 293, 441–451 (2015). https://doi.org/10.1007/s00396-014-3422-6

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  • DOI: https://doi.org/10.1007/s00396-014-3422-6

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