Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abdelmoneem MA, Mahmoud M, Zaky A et al (2018) Dual-targeted casein micelles as green nanomedicine for synergistic phytotherapy of hepatocellular carcinoma. J Control Release 287:78–93
Abe H, Goto M, Kamiya N (2010) Enzymatic single-step preparation of multifunctional proteins. Chem Commun (Camb) 46:7160–7162
Abu H, Higashi T, Anno T et al (2010) Potential use of gamma-cyclodextrin polypseudorotaxane hydrogels as an injectable sustained release system for insulin. Int J Pharm 392:83–91
Alibolandi M, Alabdollah F, Sadeghi F et al (2016) Dextran-b-poly(lactide-co-glycolide) polymersome for oral delivery of insulin: in vitro and in vivo evaluation. J Control Release 227:58–70
Chen S-C, Wu Y-C, Mi F-L et al (2004) A novel pH-sensitive hydrogel composed of N,O-carboxymethyl chitosan and alginate cross-linked by genipin for protein drug delivery. J Control Release 96:285–300
Elzoghby AO, Abo El-Fotoh E-F, Elgindy NA (2011) Casein-based formulations as promising controlled release drug delivery systems. J Control Release 153:206–216
Ghahremankhani AA, Dorkoosh F, Dinarvand R (2007) PLGA-PEG-PLGA tri-block copolymers as an in-situ gel forming system for calcitonin delivery. Polym Bull 59:637–646
Giri TK, Thakur A, Tripathi DK (2016) Biodegradable hydrogel bead of casein and modified xanthan gum for controlled delivery of theophylline. Curr Drug Therapy 11:150–162
Hoare TR, Kohane DS (2008) Hydrogels in drug delivery: progress and challenges. Polymer 49:1993–2007
Kajthunyakarn W, Sakloetsakun D, Pongjanyakul T (2018) Sodium caseinate-magnesium aluminum silicate nanocomposite films for modified-release tablets. Mater Sci Eng C 92:827–839
Khameneh B, Momen-Nejad M, Tafaghodi M (2014) In vivo evaluation of mucoadhesive properties of nanoliposomal formulations upon coating with trimethylchitosan polymer. Nanomed J 1:147–154
Khameneh B, Jaafari MR, Hassanzadeh-Khayyat M et al (2015) Preparation, characterization and molecular modeling of PEGylated human growth hormone with agonist activity. Int J Biol Macromol 80:400–409
Khameneh B, Saberi MR, Hassanzadeh-Khayyat M et al (2016) Evaluation of physicochemical and stability properties of human growth hormone upon enzymatic PEGylation. J Appl Biomed 14:257–264
Khodaverdi E, Heidari Z, Tabassi SA et al (2015) Injectable supramolecular hydrogel from insulin-loaded triblock PCL–PEG–PCL copolymer and gamma-cyclodextrin with sustained-release property. AAPS PharmSciTech 16:140–149
Khodaverdi E, Javan M, Tabassi SAS et al (2017) Sustained drug delivery system for insulin using supramolecular hydrogels composed of tri-block copolymers. J Pharmac Investig 47:263–273
Kruif CG, Anema SG, Zhu C et al (2015) Water holding capacity and swelling of casein hydrogels. Food Hydrocolloids 44:372–379
Li J, Loh XJ (2008) Cyclodextrin-based supramolecular architectures: syntheses, structures, and applications for drug and gene delivery. Adv Drug Deliv Rev 60:1000–1017
Li NN, Fu CP, Zhang LM (2014) Using casein and oxidized hyaluronic acid to form biocompatible composite hydrogels for controlled drug release. Mater Sci Eng C 36:287–293
Mcclements DJ (2018) Encapsulation, protection, and delivery of bioactive proteins and peptides using nanoparticle and microparticle systems: a review. Adv Colloid Interface Sci 253:1–22
Mohajer M, Khameneh B, Tafaghodi M (2014) Preparation and characterization of PLGA nanospheres loaded with inactivated influenza virus, CpG-ODN and Quillaja saponin. Iran J Basic Med Sci 17:722–726
Mukhopadhyay P, Kundu PP (2015) Chitosan-graft-PAMAM-alginate core-shell nanoparticles: a safe and promising oral insulin carrier in an animal model. RSC Adv 5:93995–94007
Nishinari K, Zhang H, Ikeda S (2000) Hydrocolloid gels of polysaccharides and proteins. Curr Opin Colloid Interface Sci 5:195–201
Picchio ML, Cuggino JC, Nagel G et al (2018) Crosslinked casein-based micelles as a dually responsive drug delivery system. Polym Chem 9:3499–3510
Pirouzmand H, Khameneh B, Tafaghodi M (2017) Immunoadjuvant potential of cross-linked dextran microspheres mixed with chitosan nanospheres encapsulated with tetanus toxoid. Pharm Biol 55:212–217
Song F, Zhang L, Yang C et al (2009) Genipin-crosslinked casein hydrogels for controlled drug delivery. Int J Pharm 373:41–47
Song F, Zhang L, Shi JF et al (2010) Novel casein hydrogels: formation, structure and controlled drug release. Colloids Surf B Biointerfaces 79:142–148
Tang Ch, Jiang Y, Wen Q et al (2005) Effect of transglutaminase treatment on the properties of cast films of soy protein isolates. J Biotechnol 120:296–307
Wei Y, Xie R, Lin Y et al (2016) Structure formation in pH-sensitive hydrogels composed of sodium caseinate and N,O-carboxymethyl chitosan. Int J Biol Macromol 89:353–359
Yin W, Su R, Qi W et al (2012) A casein–polysaccharide hybrid hydrogel cross-linked by transglutaminase for drug delivery. J Mater Sci 47:2045–2055
Zu Y, Zhang Y, Zhao X et al (2012) Preparation and characterization of chitosan-polyvinyl alcohol blend hydrogels for the controlled release of nano-insulin. Int J Biol Macromol 50:82–87
Acknowledgements
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.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
All authors declare that there is no conflict of interest in this study.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Khodaverdi, E., Maftouhian, S., Aliabadi, A. et al. Casein-based hydrogel carrying insulin: preparation, in vitro evaluation and in vivo assessment. J. Pharm. Investig. 49, 635–641 (2019). https://doi.org/10.1007/s40005-018-00422-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40005-018-00422-y