Casein-based hydrogel carrying insulin: preparation, in vitro evaluation and in vivo assessment

  • Elham Khodaverdi
  • Sepehr Maftouhian
  • Ali Aliabadi
  • Mohammad Hassanzadeh-Khayyat
  • Fatemeh Mohammadpour
  • Bahman KhamenehEmail author
  • Farzin HadizadehEmail author
Original Article


Hydrogels show great potential particularly in the development of drug delivery because of their desirable properties. The enzymatic crosslinked casein hydrogel is a new generation and has received great attention for drug delivery. In the present study, the enzymatic crosslinked casein hydrogel containing insulin was prepared and in vitro and in vivo evaluations were assessed. The hydrogels were also evaluated using differential scanning calorimeter; X-ray diffraction; Scanning electron microscopy and Atomic force microscopy methods. The rheological and releasing behaviors at different media were also investigated. The secondary structure of insulin was assayed by CD method and finally, the hypoglycemic effects were tested in the diabetic rats. Hydrogel showed a three-dimensional porous structure. Rheographs indicated the combination of thixotropic and pseudoplastic behaviors. In vitro release studies confirmed that insulin released in acidic condition slowly, however, in neutral and alkaline environments insulin rapidly released. The structure of insulin preserved following release. Hypoglycemic effects were observed by oral administration of insulin-loaded hydrogel. Thus, the enzymatic crosslinked hydrogel can be considered as a good candidate for oral delivery of insulin.


Hydrogel Casein Transglutaminase Insulin Oral route Hypoglycemic activity 



This study was supported by a grant from Mashhad University of Medical Sciences for the research project with approval number of 920188. The results described in this paper are part of a Pharm.D. thesis.

Compliance with ethical standards

Conflict of interest

All authors declare that there is no conflict of interest in this study.

Supplementary material

40005_2018_422_MOESM1_ESM.docx (117 kb)
Supplementary material 1 (DOCX 117 KB)


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Copyright information

© The Korean Society of Pharmaceutical Sciences and Technology 2018

Authors and Affiliations

  1. 1.Targeted Drug Delivery Research Center, School of PharmacyMashhad University of Medical SciencesMashhadIran
  2. 2.Department of Pharmaceutics, School of PharmacyMashhad University of Medical SciencesMashhadIran
  3. 3.Students Research Committee, School of PharmacyMashhad University of Medical SciencesMashhadIran
  4. 4.Department of Medicinal Chemistry, School of PharmacyMashhad University of Medical SciencesMashhadIran
  5. 5.Pharmaceutical Research Center, Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran
  6. 6.Department of Pharmaceutical Nanotechnology, School of PharmacyMashhad University of Medical SciencesMashhadIran
  7. 7.Department of Pharmaceutical Control, School of PharmacyMashhad University of Medical SciencesMashhadIran
  8. 8.Biotechnology Research Center, Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran

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