Skip to main content
SpringerLink
Log in

Evaluation of poly(hydroxyethyl acrylate/itaconic acid) hydrogels for controlled delivery of transition metal complexes with Oxaprozin as potential antiproliferative agents

  • Original Paper
  • Published:
Journal of Materials Science Aims and scope Submit manuscript

Abstract

A series of dual-sensitive poly(2-hydroxyethyl acrylate/itaconic acid) (P(HEA/IA)) hydrogels were synthesized and evaluated as drug delivery systems for potential antiproliferative agents. Investigated hydrophobic compounds, Mn(II) and Zn(II) complexes with Oxaprozin, were efficiently loaded into the P(HEA/IA) hydrogels, which was confirmed by FTIR and UV–Vis spectroscopy. Swelling studies, conducted in the physiological pH range of 2.20–8.00 and in temperature range of 30–50 °C, demonstrated that loaded transition metal complexes in P(HEA/IA) hydrogels did not annul pH and temperature sensitivity of the hydrogels. In vitro antiproliferative activity of Mn(II) and Zn(II) complexes with Oxaprozin against human cervical (HeLa) and melanoma cancer (Fem X) cell lines was tested. Results of in vitro release study investigated at different pH conditions confirmed P(HEA/IA) hydrogels as a highly effective pH-triggered drug delivery system for hydrophobic antiproliferative agents. These performances indicate that P(HEA/IA) hydrogels loaded with transition metal complexes can be further studied as a promising candidate for anticancer therapy, as well as for targeted treatment of intestine/colon cancers.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108

    Article  Google Scholar 

  2. Peto J (2001) Cancer epidemiology in the last century and the next decade. Nature 411:390–395

    Article  Google Scholar 

  3. Choedon T, Mathan G, Arya S, Kumar VL, Kumar V (2006) Anticancer and cytotoxic properties of the latex of Calotropis procera in a transgenic mouse model of hepatocellular carcinoma. World J Gastroeterol 12:2517–2522

    Google Scholar 

  4. Goodarzi N, Varshochian R, Kamalinia G, Atyabi F, Dinarvand R (2013) A review of polysaccharide cytotoxic drug conjugates for cancer therapy. Carbohydr Polym 92:1280–1293

    Article  Google Scholar 

  5. He XJ, Zhang Y, Fan L, Zhao Y, Xu T, Nie Z, Li X, Huang Z, Lu B, Xu P (2015) Synthesis and in vitro evaluation of a hyaluronic acid-quantum dots-melphalan conjugate. Carbohydr Polym 121:132–139

    Article  Google Scholar 

  6. Cheng W, Gu L, Ren W, Liu Y (2014) Stimuli-responsive polymers for anti-cancer drug delivery. Mat Sci Eng C 45:600–608

    Article  Google Scholar 

  7. Rafique S, Idrees M, Nasim A, Akbar H, Athar A (2010) Transition metal complexes as potential therapeutic agents. Biotechnol Mol Biol Rev 5:38–45

    Google Scholar 

  8. Kopf-Maier P (1994) Complexes of metals other than platinum as antitumor agents. Eur J Clin Pharmacol 47:1–16

    Article  Google Scholar 

  9. Iizuka Y, Sakurai E, Tanaka Y (2001) Effects of trace element deficiency on drug metabolizing enzymes in rats. Riken Rev 35:3–4

    Google Scholar 

  10. Lippard SJ, Berg JM (1994) Principles of bioinorganic chemistry. University Science Books, Mill Valley

    Google Scholar 

  11. Szilagyi RK, Bryngelson PA, Maroney MJ, Hedman B, Hodgson KO, Solomon EI (2004) S K-edge X-ray absorption spectroscopic investigation of the Ni-containing superoxide dismutase active site: new structural insight into the mechanism. J Am Chem Soc 126:3018–3019

    Article  Google Scholar 

  12. Kobayashi M, Shimizu S (1999) Cobalt proteins. Eur J Biochem 261:1–9

    Article  Google Scholar 

  13. Baron JA (2003) Epidemiology of non-steroidal anti-inflammatory drugs and cancer. Prog Exp Tumor Res 37:1–24

    Google Scholar 

  14. Ettarh R, Cullen A, Calamai A (2010) NSAIDs and cell proliferation in colorectal cancer. Pharmaceuticals 3:2007–2021

    Article  Google Scholar 

  15. Lay P Hambley T, (2007) WO Patent 109843 2007

  16. Božić BDj, Rogan JR, Poleti DD, Trišović NP, Božić BDj, Ušćumlić GS (2012) Synthesis, Characterization and Antiproliferative Activity of Transition Metal Complexes with 3-(4,5-Diphenyl-1,3-oxazol-2-yl)propanoic Acid (Oxaprozin). Chem Pharm Bull 60:865–869

    Article  Google Scholar 

  17. Babić MM, Antić KM, Vuković JSJ, Božić BĐ, Davidović SZ, Filipović JM, Tomić SLj (2015) Oxaprozin/poly(2-hydroxyethyl acrylate/itaconic acid) hydrogels: morphological, thermal, swelling, drug release and antibacterial properties. J Mater Sci 50:906–922. doi:10.1007/s10853-014-8651z

    Article  Google Scholar 

  18. Brown K (1971) Oxazoles, US patent 3,578,671

  19. Bell CL, Peppas NA (1995) Measurement of swelling force in ionic polymer networks. III. Swelling force of interpolymer complexes. J Control Release 37:277–280

    Article  Google Scholar 

  20. Peppas NA (1985) Analysis of Fickian and non-Fickian drug release from polymer. Pharm Acta Helv 60:110–111

    Google Scholar 

  21. Wu CL, He H, Gao HJ, Liu G, Ma RJ, An YL, Shi LQ (2010) Synthesis of Fe3O4[SiO2]polymer nanoparticles for controlled drug release. Sci China Chem 53:514–518

    Article  Google Scholar 

  22. Yu ZW, Quinn PJ (1994) Dimethyl sulphoside: a review of its applications in cell biology. Biosci Rep 14:259–281

    Article  Google Scholar 

  23. Higuchi T (1963) Mechanism of sustained-action medication: theoretical analysis of rate of release of solid drugs dispersed in soled matrices. J Pharm Sci 52:1145–1148

    Article  Google Scholar 

  24. Peppas NA, Sahlin JJ (1989) A simple equation for the description of solute release III. Coupling of diffusion and relaxation. Int J Pharm 57:169–172

    Article  Google Scholar 

  25. Yamoaka K, Nakagawa T, Uno T (1978) Application of the Akaike information criterion (AIC) in the evaluation of linear pharmacokinetics equations. J Pharmacokinet Biopharm 6:165–175

    Article  Google Scholar 

  26. Sadaf Y, Saqib A, Bushra M, Fiaz A, Saira S (2009) Interaction of naproxen with transition metals: synthesis, characterization, antiinflammatory activity and kinetic studies. J Coord Chem 62:3463–3470

    Article  Google Scholar 

  27. Asmarandei I, Fundueanu G, Cristea M, Harabagiu V, Constantin M (2013) Thermo- and pH-sensitive interpenetrating poly(N-isopropylacrylamide)/carboxymethyl pullulan network for drug delivery. J Polym Res 20:293–300

    Article  Google Scholar 

  28. Ruan G, Feng SS (2003) Preparation and characterization of poly(lactic-acid)-poly(ethylene glycol)-poly(lactic acid)(PLAPEG- PLA) microspheres for controlled release of paclitaxel. Biomaterials 24:5037–5044

    Article  Google Scholar 

  29. Sant VP, Smith D, Leroux JC (2005) Enhancement of oral bioavailability of poorly water-soluble drugs by poly(ethylene glycol)-block-poly(alkyl acrylate-co-methacrylic acid) self-assemblies. J Control Release 104:289–300

    Article  Google Scholar 

  30. Luo Y-L, Huang R-J, Xu F, Chen Y-S (2014) pH-Sensitive biodegradable PMAA2-b-PLA-b-PMAA2 H-type multiblock copolymer micelles: synthesis, characterization, and drug release applications. J Mater Sci 49:7730–7741. doi:10.1007/s10853-014-8483-x

    Article  Google Scholar 

  31. Ritger PL, Peppas NA (1987) A simple equation for description of solute release I. Fickian and non-Fickian release from nonswellable devices in the form of slabs, spheres, cylinders or discs. J Control Release 5:23–36

    Article  Google Scholar 

Download references

Acknowledgements

This work has been supported by the Ministry for Education, Science and Technological Development of the Republic of Serbia (Grants No. 172062 and 172013).

Author information

Authors and Affiliations

  1. Faculty of Technology and Metallurgy, University of Belgrade, Karnegijeva 4, Belgrade, Serbia

    Marija M. Babić, Bojan Đ. Božić, Jovanka M. Filipović, Gordana S. Ušćumlić & Simonida Lj. Tomić

  2. Faculty of Biology, University of Belgrade, Studentski trg 3, Belgrade, Serbia

    Biljana Đ. Božić

Authors
  1. Marija M. Babić
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bojan Đ. Božić
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Biljana Đ. Božić
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jovanka M. Filipović
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gordana S. Ušćumlić
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Simonida Lj. Tomić
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Simonida Lj. Tomić.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Babić, M.M., Božić, B.Đ., Božić, B.Đ. et al. Evaluation of poly(hydroxyethyl acrylate/itaconic acid) hydrogels for controlled delivery of transition metal complexes with Oxaprozin as potential antiproliferative agents. J Mater Sci 50, 6208–6219 (2015). https://doi.org/10.1007/s10853-015-9179-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10853-015-9179-6

Keywords

Search

Navigation