Skip to main content
Log in

Poly(amino acid)-based nanogel by horseradish peroxidase catalyzed crosslinking in an inverse miniemulsion

  • Original Contribution
  • Published:
Colloid and Polymer Science Aims and scope Submit manuscript

Abstract

We present an investigation of horseradish peroxidase (HRP)/H2O2-mediated crosslinking in an inverse miniemulsion for the successful preparation of a stable colloidal nanogel from a poly(amino acid)-based polymer precursor. The precursor was obtained by the aminolysis of polysuccinimide with aminoethan-2-ol and tyramine, resulting in a poly(α,β-N-(2-hydroxyethyl)-D,L-aspartamide-co-N-(2-(4-hydroxyphenyl)ethyl)-D,L-aspartamide) polymer (PHEA-Tyr). Various concentrations of the PHEA-Tyr in aqueous solution with HRP were emulsified in the presence of cyclohexane and SPAN 80. The addition of a hydrogen peroxide solution induced crosslinking between the polymer chains via the phenol groups (Tyr) and targeted nanogel formation. The hydrodynamic radii (R h 0), mean size documented by hydrodynamic radius (R h ), and morphology of the nanoparticles were investigated by dynamic light scattering (DLS) measurements, nanoparticle tracking analysis (NTA), and cryogenic transmission electron microscopy (cryo-TEM). It was found out that nanoparticle radius, morphology, and architecture of the nanogel could be regulated by the initial concentration of the precursor.

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.

Scheme 1
Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Vinogradov S, Batrakova E, Kabanov A (1999) Poly(ethylene glycol)−polyethyleneimine nanogel particles: novel drug delivery systems for antisense oligonucleotides. Colloid Surf B 16:291–304

    Article  CAS  Google Scholar 

  2. Soni KS, Desale SS, Bronich TK (2016) Nanogels: an overview of properties, biomedical applications and obstacles to clinical translation. J Control Release 240:109–126

    Article  CAS  Google Scholar 

  3. Zhang X, Malhotra S, Molina M, Haag R (2015) Micro- and nanogels with labile crosslinks—from synthesis to biomedical applications. Chem Soc Rev 44:1948–1973

    Article  CAS  Google Scholar 

  4. Iwasaki Y, Kondo JI, Kuzuya A, Moriyama R (2016) Crosslinked duplex DNA nanogels that target specified proteins. Sci Technol Adv Mat 17:285–292

    Article  CAS  Google Scholar 

  5. Pujana MA, Pérez-Álvarez L, Iturbe LCC, Katime I (2012) Water dispersible pH-responsive chitosan nanogels modified with biocompatible crosslinking-agents. Polymer 53:3107–3116

    Article  CAS  Google Scholar 

  6. Singh S, Möller M, Pich A (2013) Biohybrid nanogels. J Polym Sci Pol Chem 51:3044–3057

    Article  CAS  Google Scholar 

  7. Neamtu I, Rusu AG, Diaconu A, Nita LE, Chiriac AP (2017) Basic concepts and recent advances in nanogels as carriers for medical application. Drug Deliv 24:539–557

    Article  CAS  Google Scholar 

  8. Meléndez-Ortiz HI, Peralta RD, Bucio E, Zerrweck-Maldonado L (2014) Preparation of stimuli-responsive nanogels of poly[2-(dimethylamino) ethyl methacrylate] by heterophase and microemulsion polymerization using gamma radiation. Polym Eng Sci 54:1625–1631

    Article  Google Scholar 

  9. Oh JK, Siegwart DJ, Lee HI, Sherwood G, Peteanu L, Hollinger JO, Kataoka K, Matyjaszewski K (2007) Biodegradable nanogels prepared by atom transfer radical polymerization as potential drug delivery carriers: synthesis, biodegradation, in vitro release, and bioconjugation. J Am Chem Soc 129:5939–5945

    Article  CAS  Google Scholar 

  10. Oh JK, Bencherif SA, Matyjaszewski K (2009a) Atom transfer radical polymerization in inverse miniemulsion: a versatile route toward preparation and functionalization of microgels/nanogels for targeted drug delivery applications. Polymer 50:4407–4423

    Article  CAS  Google Scholar 

  11. Bhuchar N, Sunasee R, Ishihara K, Thundat T, Narain R (2012) Degradable thermoresponsive nanogels for protein encapsulation and controlled release. Bioconjug Chem 23:75–83

    Article  CAS  Google Scholar 

  12. Averick SE, Magenau AJD, Simakova A, Woodman BF, Seong A, Mehl RA, Matyjaszewski K (2011) Covalently incorporated protein-nanogels using AGET ATRP in an inverse miniemulsion. Polym Chem 2:1476–1478

    Article  CAS  Google Scholar 

  13. Oh JK, Lee DI, Park JM (2009b) Biopolymer-based microgels/nanogels for drug delivery applications. Prog Polym Sci 34:1261–1282

    Article  CAS  Google Scholar 

  14. Klinger D, Landfester K (2011) Dual stimuli-responsive poly(2-hydroxyethyl methacrylate-co-methacrylic acid) microgels based on photo-cleavable cross-linkers: pH-dependent swelling and light-induced degradation. Macromolecules 44:9758–9772

    Article  CAS  Google Scholar 

  15. McAllister K, Sazani P, Adam M, Cho MJ, Rubinstein M, Samulski RJ, DeSimone JM (2002) Polymeric nanogels produced via inversion microemulsion polymerization as potential gene and antisense delivery agents. J Am Chem Soc 124:15198–15207

    Article  CAS  Google Scholar 

  16. Sanson N, Rieger J (2010) Synthesis of nanogels/microgels by conventional and controlled radical crosslinking copolymerization. Polym Chem 1:965–977

    Article  CAS  Google Scholar 

  17. Yildrim T, Rinkenauer AC, Weber C, Traeger A, Schubert S, Schubert US (2015) RAFT made methacrylate copolymers for reversible pH-responsive nanoparticles. J Polym Sci Pol Chem 53:2711–2721

    Article  Google Scholar 

  18. Gao H, Matyjaszewski K (2008) Synthesis of star polymers by a new “core-first” method: sequential polymerization of cross-linker and monomer. Macromolecules 41:1118–1125

    Article  CAS  Google Scholar 

  19. Bencherif SA, Washburn NR, Matyjaszewski K (2009) Synthesis by AGET ATRP of degradable nanogel precursors for in situ formation of nanostructured hyaluronic acid hydrogel. Biomacromolecules 10:2499–2507

    Article  CAS  Google Scholar 

  20. Graff RW, Shi Y, Wang X, Gao H (2009) Comparison of loading efficiency between hyperbranched polymers and cross-linked nanogels at various branching densities. Macromol Rapid Commun 36:2076–2082

    Article  Google Scholar 

  21. Landfester K, Willert M, Antonietti M (2000) Preparation of polymer particles in nonaqueous direct and inverse miniemulsions. Macromolecules 33:2370–2376

    Article  CAS  Google Scholar 

  22. Capek I (2010) On inverse miniemulsion polymerization of conventional water-soluble monomers. Adv Colloid Interf Sci 156:35–61

    Article  CAS  Google Scholar 

  23. Dou XQ, Feng CL (2017) Amino acids and peptide-based supramolecular hydrogels for three-dimensional cell culture. Adv Mater 29:1604062

    Article  Google Scholar 

  24. Svobodová J, Proks V, Karabiyik Ö, Koyuncu ACÇ, Köse GT, Rypáček F, Studenovská H (2017) Poly(amino acid)-based fibrous scaffolds modified with surface-pendant peptides for cartilage tissue engineering. J Tissue Eng Regen Med 11:831–842

    Article  Google Scholar 

  25. Park CW, Yang HM, Woo MA, Lee KS, Kim JD (2017) Completely disintegrable redox-responsive poly(amino acid) nanogels for intracellular drug delivery. J Ind Eng Chem 45:182–188

    Article  CAS  Google Scholar 

  26. Wu DQ, Cui HC, Zhu J, Qin XH, Tie T (2016) Novel amino acid based nanogel conjugated suture for antibacterial application. J Mater Chem B 4:2606–2613

    Article  CAS  Google Scholar 

  27. Pitarresi G, Tomarchio V, Cavallaro G, Giammona G (1996) α,β-poly(N-hydroxy)-DL-aspartamide hydrogels as drug delivery devices. J Bioact Compat Polym 11:328–340

    Article  CAS  Google Scholar 

  28. Giammona G, Pitarresi G, Tomarchio V, Cacciaguerra S, Govoni P (1997) A hydrogel based on a polyaspartamide: characterization and evaluation of in-vivo biocompatibility and drug release in the rat. J Pharm Pharmacol 49:1051–1056

    Article  CAS  Google Scholar 

  29. Mandracchia D, Pitarresi G, Palumbo FS, Carlisi B, Giammona G (2004) pH-sensitive hydrogel based on a novel photocross-linkable copolymer. Biomacromolecules 5:1973–1982

    Article  CAS  Google Scholar 

  30. Rypáček F, Drobnik J, Chmelař V, Kálal J (1982) The renal excretion and retention of macromolecules. The chemical structure effect. Pflügers Arch 392:211–217

    Article  Google Scholar 

  31. Bae JW, Choi JH, Lee Y, Park D (2015) Horseradish peroxidase-catalysed in situ-forming hydrogels for tissue-engineering applications. J Tissue Eng Regen Med 9:1225–1232

    Article  CAS  Google Scholar 

  32. Neri P, Antoni G, Benvenuti F, Cocola F, Gazzei G (1973) Synthesis of α,β-poly [(2-hydroxyethyl)-DL-aspartamide], a new plasma expander. J Med Chem 16:893–897

    Article  CAS  Google Scholar 

  33. Jakeš J (1995) Regularized positive exponential sum (REPES) program—a way of inverting Laplace transform data obtained by dynamic light scattering. Collect Czechoslov Chem Commun 60:1781–1797

    Article  Google Scholar 

  34. Cavallaro G, Pitarresi G, Giammona G (2004) Advanced biomaterials for medical applications. Kluwer Academic Publishers, Dordrecht

    Google Scholar 

  35. Coviello T, Yuguchi Y, Kajiwara K, Giammona G, Cavallaro G, Alhaique F, Palleschi A (1998) Conformational analysis of α,β-poly(N-hydroxyethyl)-DL-aspartamide (PHEA) and α,β-polyasparthydrazide (PAHy) polymers in aqueous solution. Polymer 39:4159–4164

    Article  CAS  Google Scholar 

  36. Jansen TGT, Meuldijk J, Lovell PA, van Herk AM (2016) On the miniemulsion polymerization of very hydrophobic monomers initiated by a completely water-insoluble initiators: thermodynamics, kinetics, and mechanism. J Polym Sci Polym Chem 54:2731–2745

    Article  CAS  Google Scholar 

  37. Filipe V, Hawe A, Jiskoot W (2010) Critical evaluation of nanoparticle tracking analysis (NTA) by NanoSight for the measurement of nanoparticles and protein aggregates. Pharm Res 27:796–810

    Article  CAS  Google Scholar 

  38. Gonzáles de Torre I, Quintanilla L, Pinedo-Martín G, Alonso M, Rodríguez-Cabello JC (2014) Nanogel formation from dilute solutions of clickable elastine-like recombinamers and its dependence on temperature: two fractal gelation modes. ACS Appl Mater Interfaces 6:14509–14515

    Article  Google Scholar 

  39. Wang R, Xu DI, Liang L, Xu TT, Liu W, Ouyang PK, Chi B, Xu H (2016) Enzymatically crosslinked epsilon-poly-L-lysine hydrogels with inherent antibacterial properties for wound infection prevention. RSC Adv 6:8620–8627

    Article  CAS  Google Scholar 

  40. Koul V, Mohamed R, Kuckling D, Adler HJP, Choudhary V (2011) Interpenetrating polymer network (IPN) nanogels based on gelatin and poly(acrylic acid) by inverse miniemulsion technique: synthesis and characterization. Colloid Surf B 83:204–213

    Article  CAS  Google Scholar 

  41. Wu C, Böttcher C, Haag R (2015) Enzymatically crosslinked dendritic polyglycerol nanogels for encapsulation of catalytically active proteins. Soft Matter 11:972–980

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Šálek Petr.

Ethics declarations

Financial support from the Czech Science Foundation (No. 16-02702S) is gratefully acknowledged.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Petr, Š., Jana, D., Peter, Č. et al. Poly(amino acid)-based nanogel by horseradish peroxidase catalyzed crosslinking in an inverse miniemulsion. Colloid Polym Sci 296, 995–1003 (2018). https://doi.org/10.1007/s00396-018-4318-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00396-018-4318-7

Keywords

Navigation