In the present study, injectable hydrogels based on gum tragacanth–tyramine conjugate were prepared by enzymatic oxidation of tyramine radicals in the presence of hydrogen peroxide. Then, in vitro release of bovine serum albumin and insulin as model protein drugs from this polymeric network was investigated. Also, to improve the properties of this hydrogel, a blended hydrogel composed of tyramine-conjugated gelatin and tyramine-conjugated tragacanth was prepared. Experimental results showed that the gelation time ranged from 3 to 28 s depending on the polymer and enzyme concentrations. Results of morphological investigation of hydrogels indicated that the average pore size of hydrogels varied from 120 to 160 µm. Swelling degree of hydrogels and the rate of drug release decreased by increasing of hydrogen peroxide and polymer concentrations. The release profile of drug from hydrogels followed Higuchi and Fickian diffusion mechanism. Finally, it was shown that the swelling characteristics and drug release behavior of this polymeric network could be improved by blending it with tyramine-conjugated gelatin.
PackhaeuserCBSchniedersJOsterCG. In situ forming parenteral drug delivery systems: an overview. Eur J Pharm Biopharm2004; 58: 445–455.
4.
KimSHWonCYChuCC. Synthesis and characterization of dextran-based hydrogel prepared by photocrosslinking. Carbohydr Polym1999; 40: 183–190.
5.
JinRTeixeiraLSMKrouwelsA. Synthesis and characterization of hyaluronic acid–poly(ethylene glycol) hydrogels via Michael addition: an injectable biomaterial for cartilage repair. Acta Biomater2010; 6: 1968–1977.
6.
NguyenTPLeeBT. Fabrication of oxidized alginate-gelatin-BCP hydrogels and evaluation of the microstructure, material properties and biocompatibility for bone tissue regeneration. J Biomater Appl2012; 27: 311–321.
Ruel-GariépyELerouxJ-C. In situ-forming hydrogels—review of temperature-sensitive systems. Eur J Pharm Biopharm2004; 58: 409–426.
9.
ParkM-RSeoB-BSongS-C. Dual ionic interaction system based on polyelectrolyte complex and ionic, injectable, and thermosensitive hydrogel for sustained release of human growth hormone. Biomaterials2013; 34: 1327–1336.
10.
ChungHJLeeYParkTG. Thermo-sensitive and biodegradable hydrogels based on stereocomplexed pluronic multi-block copolymers for controlled protein delivery. J Control Rel2008; 127: 22–30.
11.
JinRHiemstraCZhongZ. Enzyme-mediated fast in situ formation of hydrogels from dextran-tyramine conjugates. Biomaterials2007; 28: 2791–2800.
12.
SakaiSYamadaYZenkeT. Novel chitosan derivative soluble at neutral pH and in situ gellable via peroxidase-catalyzed enzymatic reaction. J Mater Chem2009; 19: 230–235.
13.
OgushiYSakaiSKawakamiK. Synthesis of enzymatically-gellable carboxymethylcellulose for biomedical applications. J Biosc Bioeng2007; 104: 30–33.
14.
KurisawaMChungJEYangYY. Injectable biodegradable hydrogels composed of hyaluronic acid–tyramine conjugates for drug delivery and tissue engineering. Chem Commun2005; 34: 4312–4314.
15.
SakaiSHiroseKTaguchiK. An injectable, in situ enzymatically gellable, gelatin derivative for drug delivery and tissue engineering. Biomaterials2009; 30: 3371–3377.
16.
XuKLeeFGaoSJ. Injectable hyaluronic acid-tyramine hydrogels incorporating interferon-α2a for liver cancer therapy. J Control Rel2013; 166: 203–210.
17.
WangLSBoulaireJChanPPY. The role of stiffness of gelatin-hydroxyphenylpropionic acid hydrogels formed by enzyme-mediated crosslinking on the differentiation of human mesenchymal stem cell. Biomaterials2010; 31: 8608–8616.
18.
KimKSParkSJYangJA. Injectable hyaluronic acid–tyramine hydrogels for the treatment of rheumatoid arthritis. Acta Biomater2011; 7: 666–674.
19.
JinRMoreira TeixeiraLSDijkstraPJ. Enzymatically-crosslinked injectable hydrogels based on biomimetic dextran–hyaluronic acid conjugates for cartilage tissue engineering. Biomaterials2010; 31: 3103–3113.
20.
Moreira TeixeiraLSBijlSPullyVV. Self-attaching and cell-attracting in-situ forming dextran-tyramine conjugates hydrogels for arthroscopic cartilage repair. Biomaterials2012; 33: 3164–3174.
21.
ParkKMLeeYSonJY. Synthesis and characterizations of in situ cross-linkable gelatin and 4-arm-PPO-PEO hybrid hydrogels via enzymatic reaction for tissue regenerative medicine. Biomacromolecules2012; 13: 604–611.
22.
ThanKDRahmanSUWangL. Intradiscal injection of simvastatin results in radiologic, histologic, and genetic evidence of disc regeneration in a rat model of degenerative disc disease. Spine J2014; 14: 1017–1028.
23.
GaneshNHannaCNairSV. Enzymatically cross-linked alginic–hyaluronic acid composite hydrogels as cell delivery vehicles. Int J Biol Macromol2013; 55: 289–294.
24.
BalaghiSMohammadifarMAZargaraanA. Compositional analysis and rheological characterization of gum tragacanth exudates from six species of Iranian Astragalus. Food Hydrocoll2011; 25: 1775–1784.
25.
Mohammad Amin MohammadifarSMMAmir KiumarsiPAW. Solution properties of targacanthin (water-soluble part of gum tragacanth exudate from Astragalus gossypinus). Int J Biol Macromol2006; 38: 31–39.
26.
TavakolMVasheghani-FarahaniESoleimaniM. Synthesis and characterization of an enzyme mediated in situ forming hydrogel based on gum tragacanth for biomedical applications. Iran J Biotechnol2013; 12: 15811–15811.
27.
BradfordMM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem1976; 72: 248–254.
28.
GongCYShiSDongPW. In vitro drug release behavior from a novel thermosensitive composite hydrogel based on Pluronic f127 and poly(ethylene glycol)-poly(ɛ-caprolactone)-poly(ethylene glycol) copolymer. BMC Biotechnol2009; 9: 8–21.
29.
WuD-QSunY-XXuX-D. Biodegradable and pH-sensitive hydrogels for cell encapsulation and controlled drug release. Biomacromolecules2008; 9: 1155–1162.
30.
ParkKMShinYMJoungYK. In situ forming hydrogels based on tyramine conjugated 4-Arm-PPO-PEO via enzymatic oxidative reaction. Biomacromolecules2010; 11: 706–712.
31.
LeeFChungJEKurisawaM. An injectable enzymatically crosslinked hyaluronic acid-tyramine hydrogel system with independent tuning of mechanical strength and gelation rate. Soft Matter2008; 4: 880–887.
32.
WenninkJWHNiedererKBochyńskaAI. Injectable hydrogels by enzymatic co-crosslinking of dextran and hyaluronic acid tyramine conjugates. Macromol Symp2011; 309–310: 213–221.
33.
MandalBBKapoorSKunduSC. Silk fibroin/polyacrylamide semi-interpenetrating network hydrogels for controlled drug release. Biomaterials2009; 30: 2826–2836.
34.
HenninkWETalsmaHBorchertJCH. Controlled release of proteins from dextran hydrogels. J Control Rel1996; 39: 47–55.
