Skip to main content
SpringerLink
Log in

Preparation of pH sensitive insulin-loaded nano hydrogels and evaluation of insulin releasing in different pH conditions

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

In the recent years, temperature and pH-sensitive hydrogels were developed as suitable carriers for drug delivery. In this study, four different pH-sensitive nanohydrogels were designed for an oral insulin delivery modeling. NIPAAm–MAA–HEM copolymers were synthesized by radical chain reaction with 80:8:12 ratios respectively. Reactions were carried out in four conditions including 1,4-dioxan and water as two distinct solution under nitrogen gas-flow. The copolymers were characterized with FT-IR, SEM and TEM. Copolymers were loaded with regular insulin by modified double emulsion method with ratio of 1:10. Release study carried out in pH 1.2 and pH 6.8 at 37 °C. For pH 6.8 and pH 1.2, 2 mg of the insulin loaded nanohydrogels was float in a beaker containing 100 mL of PBS with pH 6.8 and 100 mL of HCl solution with pH 1.2, respectively. Sample collection was done in different times and HPLC was used for analysis of samples using water/acetonitrile (65/35) as the mobile phase. Nanohydrogels synthesis reaction yield was 95 %, HPLC results showed that loading in 1,4-dioxan without cross-linker nanohydrogels was more than others, also indicated that the insulin release of 1,4-dioxan without cross-linker nanohydrogels at acidic pH is less, but in pH 6.8 is the most. Results showed that by opting suitable polymerization method and selecting the best nanohydrogels, we could obtain a suitable insulin loaded nanohydrogels for oral administration.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Morçöl T, Nagappan P, Nerenbaum L, Mitchell A (2004) Calcium phosphate–PEG–insulin-casein (CAPIC) particles as oral delivery systems for insulin. Int J Pharm 277(1–2):91–97

    Article  PubMed  Google Scholar 

  2. Sweetman S (ed) (2007) Martindale, the complete drug reference. Pharmaceutical Press, London Electronic version

    Google Scholar 

  3. King H, Aubert RE, Herman WH (1998) Global burden of diabets 1995–2005: prevalence, numerical, estimates and projection. Diabets Care 21:1414–1431

    Article  CAS  PubMed  Google Scholar 

  4. Akhter DT, Nijhu RS (2012) Diabetes mellitus: a journey of insulin. Int Curr Pharm J 1(2):32–42

    Article  CAS  Google Scholar 

  5. Morishita M, Goto T, Nakamura K, Lowman AM, Takayama K, Peppas NA (2006) Novel oral insulin delivery systems based on complexation polymer hydrogels: single and multiple administration studies in type 1 and 2 diabetic rats. J Control Release 110:587–594

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Kinesh VP, Neelam DP, Punit BP, Bhavesh SB, Pragna KS (2010) Novel approaches for oral delivery of insulin and current status of oral insulin products. Int J Pharm Sci Nanotechnol 3(3):1057–1064

    CAS  Google Scholar 

  7. Davaran S, Jafari B, Rafie F (2011) Pharmaceutical sciences, oral insulin: a review on its current condition and future aspects. Pharm Sci 17(3):151–162

    Google Scholar 

  8. Carino GP, Mathiowitz E (1999) Oral insulin delivery. J Adv Drug Deliv Rev 35:249–257

    Article  CAS  Google Scholar 

  9. Pan YJ, Chen YY, Wang DR, Wei Ch, Guo J, Lu DR, Chu CC, Wang CC (2012) Redox/pH dual stimuli-responsive biodegradable nanohydrogels with varying responses to dithiothreitol and glutathione for controlled drug release. Biomaterials 33(27):6570–6579

    Article  CAS  PubMed  Google Scholar 

  10. Lowman AM (1999) Oral delivery of insulin using pH sensitive complexation gels. J Pharm Sci 88(9):933–937

    Article  CAS  PubMed  Google Scholar 

  11. Peppas NA (2004) Devices based on intelligent biopolymers for oral protein delivery. Int J Pharm 277:11–17

    Article  CAS  PubMed  Google Scholar 

  12. Ramkisson-Ganorkar C (1999) Modulating insulin release profile from pH/thermosensitive polymeric beads through polymer molecular weight. J Control Release 59(3):287–298

    Article  Google Scholar 

  13. Reis CP, Ribeiro AJ, Neufeld RJ, Veiga F (2007) Alginate microparticles as novel carrier for oral insulin delivery. J Biotechnol Bioeng 96(5):97

    Article  Google Scholar 

  14. Gupta S, Kuckling D, Kretschmer K, Choudhary V, Rgen Adler H (2006) Synthesis and characterization of stimuli-sensitive micro- and nanohydrogels based on photocrosslinkable poly(dimethylaminoethyl methacrylate). J Polym Sci Part A Polym Chem. doi:10.1002/pola.21846

    Google Scholar 

  15. Akiyosh K, Kobayashi S, Schichibe S, Mix D, Baudys M, Kim SW, Sunamoto J (1998) Self-assembled hydrogel nanoparticle of cholesterol-bearing pullulan as a carrier of protein drugs: complexation and stabilization of insulin. J. Control Release 54(3):313–320

    Article  Google Scholar 

  16. Na K, Bae YH (2004) Self-assembled hydrogel nanoparticles responsive to tumor extracellular pH from pullulan derivative/sulfonamide conjugate: characterization, aggregation and adriamycin release in vitro. Pharm Res 19(5):681–688

    Article  Google Scholar 

  17. Argentiere S, Blasi L, Ciccarella G, Barbarella G, Cingolani R, Gigli G (2010) Nanogels of poly (acrylic acid): uptake and release behavior with fluorescent oligothiophene-labeled bovine serum albumin. J Appl Polym Sci 116(5):2808–2815

    CAS  Google Scholar 

  18. Liu KH, Liu TY, Chen SY, Liu DM (2008) Drug release behavior of chitosan–montmorillonite nanocomposite hydrogels following electrostimulation. Acta Biomater 4:1038–1045

    Article  CAS  PubMed  Google Scholar 

  19. Sahiner N, Godbey WT, McPherson GL, John VT (2006) Microgel, nanogel and hydrogel–hydrogel semi-IPN composites for biomedical applications: synthesis and characterization. Colloid Polym Sci 284:1121–1129. doi:10.1007/s00396-006-1489-4

    Article  CAS  Google Scholar 

  20. Üzüm Ö, Karadağ E (2007) Swelling characterization of poly (acrylamide-co-N-vinylimidazole) hydrogels crosslinked by TMPTA and semi-IPN’s with PEG. J Polym Res 14:483–488

    Article  Google Scholar 

  21. Jafari B, Rafie F, Davaran S (2011) Preparation and characterization of a novel smart polymeric hydrogel for drug delivery of insulin. Bio Impacts 1(2):135–143

    CAS  Google Scholar 

  22. Geever LM, Devine DM, Nugent MJD, Kennedy JE, Lyons JG, Higginbotham CL (2006) The synthesis, characterisation, phase behaviour and swelling of temperature sensitive physically crosslinked poly (1-vinyl-2-pyrrolidinone)/poly (N-isopropylacrylamide) hydrogels. Eur Polym J 42(1):69–80

    Article  CAS  Google Scholar 

  23. Hsiue GH, Hsu SH, Yang CC, Lee SH, Yang IK (2002) Preparation of controlled release ophthalmic drops, for glaucoma therapy using thermosensitive poly-N-isopropylacrylamide. Biomaterials 23:457–462

    Article  CAS  PubMed  Google Scholar 

  24. Hsiue GH, Chang RW, Wang CH, Lee SH (2003) Development of in situ thermosensitive drug vehicles for glaucoma therapy. Biomaterials 24:2423–2430

    Article  CAS  PubMed  Google Scholar 

  25. Matsumaru Y, Hyodo A, Nose T, Ito S, Hirano T, Ohashi S (1996) Application of thermosensitive polymers as a new embolic material for intravascular neurosurgery. J Biomater Sci Polym Ed 7:795–804

    Article  CAS  PubMed  Google Scholar 

  26. Lee BH, Leon C, McLemore R, Macias JV, Vernon BL (2011) Synthesis and characterization of thermo-sensitive radio-opaque poly (N isopropylacrylamide-co-PEG-2-iodobenzoate). J Biomater Sci Polym Ed 22:2357–2367

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Department of Medical Nanotechnology, Faculty of Advanced Medical Science of Tabriz University for all supports provided. This work was funded by 2013 Drug Applied Research Center Grant.

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Jalil Karnoosh-Yamchi, Ali Reza Ostad-Rahimi & Mohammad Rahmati-Yamchi

  2. Bone Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Majid Mobasseri

  3. Department of Clinical Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Jalil Karnoosh-Yamchi & Mohammad Rahmati-Yamchi

  4. Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Abolfazl Akbarzadeh, Soodabeh Davaran & Kazem Nejati-Koshki

  5. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Hamed Hamishehkar & Roya Salehi

  6. Plant Science Department, University of Tabriz, Tabriz, Iran

    Zahra Bahmani

  7. Aras International Branch of Tabriz University of Medical Sciences, Tabriz, Iran

    Jalil Karnoosh-Yamchi & Mohammad Rahmati-Yamchi

  8. Madani Hospital, Tabriz University of Medical Sciences, Tabriz, Iran

    Akbar Darbin

Authors
  1. Jalil Karnoosh-Yamchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Majid Mobasseri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abolfazl Akbarzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Soodabeh Davaran
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ali Reza Ostad-Rahimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hamed Hamishehkar
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Roya Salehi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zahra Bahmani
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kazem Nejati-Koshki
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Akbar Darbin
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Mohammad Rahmati-Yamchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohammad Rahmati-Yamchi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Karnoosh-Yamchi, J., Mobasseri, M., Akbarzadeh, A. et al. Preparation of pH sensitive insulin-loaded nano hydrogels and evaluation of insulin releasing in different pH conditions. Mol Biol Rep 41, 6705–6712 (2014). https://doi.org/10.1007/s11033-014-3553-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-014-3553-3

Keywords

Search

Navigation