Skip to main content
Top
Published in: Journal of Polymer Research 8/2016

01-08-2016 | Original Paper

Genipin cross-linked chitosan hydrogel for the controlled release of tetracycline with controlled release property, lower cytotoxicity, and long-term bioactivity

Authors: Wu Zhang, Guangli Ren, Hao Xu, Jinglin Zhang, Huidi Liu, Shansong Mu, Xiang Cai, Ting Wu

Published in: Journal of Polymer Research | Issue 8/2016

Log in

Activate our intelligent search to find suitable subject content or patents.

search-config
loading …

Abstract

To realize the controlled release property, lower cytotoxicity, and long-term bioactivity of tetracycline, the chitosan hydrogel had been prepared using genipin as the cross-linker and the tetracycline was in situ encapsulated. The formation process and strength of hydrogel were studied by rheological analysis, and the microtopography was observed by scanning electron microscope. It was found that the amount of genipin could modulate the physical property of the hydrogel. For in vitro release and antibacterial assays, the hydrogel could controllably release tetracycline and keep its bioactivity for a long time. The tetracycline-loaded chitosan hydrogel showed good antibacterial effect even under alkaline environment, which displayed better stability compared with free tetracycline. Moreover, the tetracycline-loaded chitosan hydrogel exhibited lower cytotoxicity than did tetracycline alone, suggesting that this tetracycline-loaded chitosan hydrogel could be a more useful dosage form than separate doses of tetracycline. The novel aspects of this study include the cytotoxicity study and the in vitro and in vivo assays, which might be useful for other researchers in this field.

Dont have a licence yet? Then find out more about our products and how to get one now:

Springer Professional "Wirtschaft+Technik"

Online-Abonnement

Mit Springer Professional "Wirtschaft+Technik" erhalten Sie Zugriff auf:

  • über 102.000 Bücher
  • über 537 Zeitschriften

aus folgenden Fachgebieten:

  • Automobil + Motoren
  • Bauwesen + Immobilien
  • Business IT + Informatik
  • Elektrotechnik + Elektronik
  • Energie + Nachhaltigkeit
  • Finance + Banking
  • Management + Führung
  • Marketing + Vertrieb
  • Maschinenbau + Werkstoffe
  • Versicherung + Risiko

Jetzt Wissensvorsprung sichern!

Springer Professional "Technik"

Online-Abonnement

Mit Springer Professional "Technik" erhalten Sie Zugriff auf:

  • über 67.000 Bücher
  • über 390 Zeitschriften

aus folgenden Fachgebieten:

  • Automobil + Motoren
  • Bauwesen + Immobilien
  • Business IT + Informatik
  • Elektrotechnik + Elektronik
  • Energie + Nachhaltigkeit
  • Maschinenbau + Werkstoffe




 

Jetzt Wissensvorsprung sichern!

Literature
1.
go back to reference Steven TC (2015) Restorative challenge: tetracycline-stained teeth. Dent Today 34:126–130 Steven TC (2015) Restorative challenge: tetracycline-stained teeth. Dent Today 34:126–130
2.
go back to reference Rok J, Buszman E, Delijewski M, Otrȩba M, Beberok A, Wrześniok DJ (2015) Effect of tetracycline and UV radiation on melanization and antioxidant tatus of melanocytes. Photoch Photobio B 148:168–173CrossRef Rok J, Buszman E, Delijewski M, Otrȩba M, Beberok A, Wrześniok DJ (2015) Effect of tetracycline and UV radiation on melanization and antioxidant tatus of melanocytes. Photoch Photobio B 148:168–173CrossRef
3.
go back to reference Aguzzi C, Sandri G, Cerezo P, Ferrari F, Rossi S, Bonferoni C, Caramella C, Viseras C (2014) A novel bioadhesive semisolid formulation containing chitosan and tetracycline/layered clay complexes for local delivery into periodontal pocket. Mater Technol 29:B108–B113CrossRef Aguzzi C, Sandri G, Cerezo P, Ferrari F, Rossi S, Bonferoni C, Caramella C, Viseras C (2014) A novel bioadhesive semisolid formulation containing chitosan and tetracycline/layered clay complexes for local delivery into periodontal pocket. Mater Technol 29:B108–B113CrossRef
4.
go back to reference Ruggiero R, Carvalho VDA, Silva LGD, Magalhães DD, Ferreira JA, Menezes HHMD, Melo PGD, Naves MM (2015) Study of in vitro degradation of cellulose acetate membranes modified and incorporated with tetracycline for use as an adjuvant in periodontal reconstitution. Ind Crop Prod 72:2–6CrossRef Ruggiero R, Carvalho VDA, Silva LGD, Magalhães DD, Ferreira JA, Menezes HHMD, Melo PGD, Naves MM (2015) Study of in vitro degradation of cellulose acetate membranes modified and incorporated with tetracycline for use as an adjuvant in periodontal reconstitution. Ind Crop Prod 72:2–6CrossRef
5.
go back to reference Reddy NS, Sowmya S, Bumgardner JD, Chennazhi KP, Biswas R, Jayakumar R (2014) Tetracycline nanoparticles loaded calcium sulfate composite beads for periodontal management. BBA-Gen Subj 1840:2080–2090CrossRef Reddy NS, Sowmya S, Bumgardner JD, Chennazhi KP, Biswas R, Jayakumar R (2014) Tetracycline nanoparticles loaded calcium sulfate composite beads for periodontal management. BBA-Gen Subj 1840:2080–2090CrossRef
6.
go back to reference Khodir WKWA, Guarino V, Alvarez-Perez MA, Cafiero C, Ambrosio L (2013) Trapping tetracycline-loaded nanoparticles into polycaprolactone fiber networks for periodontalregeneration therapy. J Bioact Compat Polym 28:258–273CrossRef Khodir WKWA, Guarino V, Alvarez-Perez MA, Cafiero C, Ambrosio L (2013) Trapping tetracycline-loaded nanoparticles into polycaprolactone fiber networks for periodontalregeneration therapy. J Bioact Compat Polym 28:258–273CrossRef
7.
go back to reference Goyal G, Garg T, Rath G, Goyal AK (2014) Current nanotechnological strategies for an effective delivery of drugs in treatment of periodontal disease. Crit Rev Ther Drug 31:89–119CrossRef Goyal G, Garg T, Rath G, Goyal AK (2014) Current nanotechnological strategies for an effective delivery of drugs in treatment of periodontal disease. Crit Rev Ther Drug 31:89–119CrossRef
8.
go back to reference Wen Y, Kolonich HR, Kruszewski KM, Giannoukakis N, Gawalt ES, Meng WS (2013) Retaining antibodies in tumors using a self-assembling injectable system. Mol Pharm 10:1035–1044CrossRef Wen Y, Kolonich HR, Kruszewski KM, Giannoukakis N, Gawalt ES, Meng WS (2013) Retaining antibodies in tumors using a self-assembling injectable system. Mol Pharm 10:1035–1044CrossRef
9.
go back to reference Ma D, Wu T, Zhang J, Lin M, Mai W, Tan S, Xue W, Cai X (2013) Supramolecular hydrogels sustained release triclosan with controlled antibacterial activity and limited cytotoxicity. Sci Adv Mater 5:1400–1409CrossRef Ma D, Wu T, Zhang J, Lin M, Mai W, Tan S, Xue W, Cai X (2013) Supramolecular hydrogels sustained release triclosan with controlled antibacterial activity and limited cytotoxicity. Sci Adv Mater 5:1400–1409CrossRef
10.
go back to reference Wen Y, Collier JH (2015) Supramolecular peptide vaccines: tuning adaptive immunity. Curr Opin Immunol 35:73–79CrossRef Wen Y, Collier JH (2015) Supramolecular peptide vaccines: tuning adaptive immunity. Curr Opin Immunol 35:73–79CrossRef
11.
go back to reference Patel AK (2015) Chitosan: emergence as potent candidate for green adhesive market. Biochem Eng J 102:74–81CrossRef Patel AK (2015) Chitosan: emergence as potent candidate for green adhesive market. Biochem Eng J 102:74–81CrossRef
12.
go back to reference Miguel SP, Ribeiro MP, Brancal H, Coutinhoa P, Correia IJ (2014) Thermoresponsive chitosan–agarose hydrogel for skin regeneration. Carbohyd Polym 111:366–373CrossRef Miguel SP, Ribeiro MP, Brancal H, Coutinhoa P, Correia IJ (2014) Thermoresponsive chitosan–agarose hydrogel for skin regeneration. Carbohyd Polym 111:366–373CrossRef
13.
go back to reference Sacco P, Travan A, Borgogna M, Paoletti S, Marsich EJ (2015) Silver-containing antimicrobial membrane based on chitosan-TPP hydrogel for the treatment of wounds. Mater Sci Mater Med 26:128CrossRef Sacco P, Travan A, Borgogna M, Paoletti S, Marsich EJ (2015) Silver-containing antimicrobial membrane based on chitosan-TPP hydrogel for the treatment of wounds. Mater Sci Mater Med 26:128CrossRef
14.
go back to reference Noppakundilograt S, Sonjaipanich K, Thongchul N, Kiatkamjornwong S (2013) Syntheses, characterization, and antibacterial activity of chitosan grafted hydrogels and associated mica-containing nanocomposite hydrogels. J Appl Polym Sci 127:4927–4938CrossRef Noppakundilograt S, Sonjaipanich K, Thongchul N, Kiatkamjornwong S (2013) Syntheses, characterization, and antibacterial activity of chitosan grafted hydrogels and associated mica-containing nanocomposite hydrogels. J Appl Polym Sci 127:4927–4938CrossRef
15.
go back to reference Delmar K, Bianco-Peled H (2015) The dramatic effect of small pH changes on the properties of chitosan hydrogels crosslinked with genipin. Carbohyd Polym 127:28–37CrossRef Delmar K, Bianco-Peled H (2015) The dramatic effect of small pH changes on the properties of chitosan hydrogels crosslinked with genipin. Carbohyd Polym 127:28–37CrossRef
16.
go back to reference Weng L, Rostambeigi N, Zantek ND, Rostamzadeh P, Bravo M, Carey J, Golzarian J (2013) An in situ forming biodegradable hydrogel-based embolic agent for interventional therapies. Acta Biomater 9:8182–8191CrossRef Weng L, Rostambeigi N, Zantek ND, Rostamzadeh P, Bravo M, Carey J, Golzarian J (2013) An in situ forming biodegradable hydrogel-based embolic agent for interventional therapies. Acta Biomater 9:8182–8191CrossRef
17.
go back to reference Ninh C, Iftikhar A, Cramer M, Bettinger CJJ (2015) Diffusion–reaction models of genipin incorporation into fibrin networks. Mater Chem B 3:4607–4615CrossRef Ninh C, Iftikhar A, Cramer M, Bettinger CJJ (2015) Diffusion–reaction models of genipin incorporation into fibrin networks. Mater Chem B 3:4607–4615CrossRef
18.
go back to reference Liu T, Liu H, Wu Z, Chen T, Zhou L, Liang Y, Ke B, Huang H, Jiang Z, Xie M, Wu T (2014) The use of poly(methacrylic acid) nanogel to control the release of amoxycillin with lower cytotoxicity. Mat Sci Eng C-Mater 43:622–629CrossRef Liu T, Liu H, Wu Z, Chen T, Zhou L, Liang Y, Ke B, Huang H, Jiang Z, Xie M, Wu T (2014) The use of poly(methacrylic acid) nanogel to control the release of amoxycillin with lower cytotoxicity. Mat Sci Eng C-Mater 43:622–629CrossRef
19.
go back to reference Ma D, Lin Q, Zhang L, Liang Y, Xue W (2014) A star-shaped porphyrin-arginine functionalized poly(L-lysine) copolymer for photo-enhanced drug and gene co-delivery. Biomaterials 35:4357–4367CrossRef Ma D, Lin Q, Zhang L, Liang Y, Xue W (2014) A star-shaped porphyrin-arginine functionalized poly(L-lysine) copolymer for photo-enhanced drug and gene co-delivery. Biomaterials 35:4357–4367CrossRef
20.
go back to reference Moura MJ, Martins SP, Duarte BP (2015) Production of chitosan microparticles cross-linked with genipin-identification of factors influencing size and shape properties. Biochem Eng J 104:82–90CrossRef Moura MJ, Martins SP, Duarte BP (2015) Production of chitosan microparticles cross-linked with genipin-identification of factors influencing size and shape properties. Biochem Eng J 104:82–90CrossRef
21.
go back to reference Zhang W, Zhou X, Liu T, Ma D, Xue W (2015) Supramolecular hydrogels co-loaded with camptothecin and doxorubicin for sustainedly synergistic tumor therapy. J Mater Chem B 3:2127–2136CrossRef Zhang W, Zhou X, Liu T, Ma D, Xue W (2015) Supramolecular hydrogels co-loaded with camptothecin and doxorubicin for sustainedly synergistic tumor therapy. J Mater Chem B 3:2127–2136CrossRef
22.
go back to reference Franson NW, Peppas NA (1983) Influence of copolymer composition on non-Fickian water transport through glassy copolymers. J Appl Polym Sci 28:1299CrossRef Franson NW, Peppas NA (1983) Influence of copolymer composition on non-Fickian water transport through glassy copolymers. J Appl Polym Sci 28:1299CrossRef
23.
go back to reference Croisier F, Sibret P, Dupont-Gillain CC, Genet MJ, Detrembleur C, Jérôme C (2015) Chitosan-coated electrospun nanofibers with antibacterial activity. J Mater Chem B 3:3508–3517CrossRef Croisier F, Sibret P, Dupont-Gillain CC, Genet MJ, Detrembleur C, Jérôme C (2015) Chitosan-coated electrospun nanofibers with antibacterial activity. J Mater Chem B 3:3508–3517CrossRef
24.
go back to reference Barreras US, Méndez FT, Martínez REM, Valencia CS, Rodríguez PRM, Rodríguez JPL (2016) Chitosan nanoparticles enhance the antibacterial activity of chlorhexidine in collagen membranes used for periapical guided tissue regeneration. Mat Sci Eng C-Mater 58:1182–1187CrossRef Barreras US, Méndez FT, Martínez REM, Valencia CS, Rodríguez PRM, Rodríguez JPL (2016) Chitosan nanoparticles enhance the antibacterial activity of chlorhexidine in collagen membranes used for periapical guided tissue regeneration. Mat Sci Eng C-Mater 58:1182–1187CrossRef
25.
go back to reference Avetta P, Nisticò R, Faga MG, D’Angelo D, Boot EA, Lamberti R, Martorana S, Calza P, Fabbri D, Magnacca G (2014) Hernia-repair prosthetic devices functionalised with chitosan and ciprofloxacin coating: controlled release and antibacterial activity. J Mater Chem B 2:5287–5294CrossRef Avetta P, Nisticò R, Faga MG, D’Angelo D, Boot EA, Lamberti R, Martorana S, Calza P, Fabbri D, Magnacca G (2014) Hernia-repair prosthetic devices functionalised with chitosan and ciprofloxacin coating: controlled release and antibacterial activity. J Mater Chem B 2:5287–5294CrossRef
26.
go back to reference Ma D, Cai X, Lin Q, Zhang J, Mai W, Tan S, Xue W, Wu T (2013) Alginate hydrogel sphere improves the alkali and heat resistances of isothiazolinones with long-term antibacterial activity. J Appl Polym Sci 130:1554–1561CrossRef Ma D, Cai X, Lin Q, Zhang J, Mai W, Tan S, Xue W, Wu T (2013) Alginate hydrogel sphere improves the alkali and heat resistances of isothiazolinones with long-term antibacterial activity. J Appl Polym Sci 130:1554–1561CrossRef
27.
go back to reference Wen Y, Liu W, Giannoukakis N, Gawalt ES, Meng WS (2014) Antibody-functionalized peptidic membranes for neutralization of allogeneic skin antigen-presenting cells. Acta Biomater 10:4759–4767CrossRef Wen Y, Liu W, Giannoukakis N, Gawalt ES, Meng WS (2014) Antibody-functionalized peptidic membranes for neutralization of allogeneic skin antigen-presenting cells. Acta Biomater 10:4759–4767CrossRef
28.
go back to reference Dang Q, Liu C, Wang Y, Yan J, Wan H, Fan B (2016) Characterization and biocompatibility of injectable microspheres-loaded hydrogel for methotrexate delivery. Carbohydr Polym 136:516–526CrossRef Dang Q, Liu C, Wang Y, Yan J, Wan H, Fan B (2016) Characterization and biocompatibility of injectable microspheres-loaded hydrogel for methotrexate delivery. Carbohydr Polym 136:516–526CrossRef
29.
go back to reference Cai X, Zhang JL, Ouyang Y, Ma D, Tan SZ, Peng YL (2013) Bacteria-adsorbed palygorskite stabilizes the quaternary phosphonium salt with specific-targeting capability, long-term antibacterial activity and lower cytotoxicity. Langmuir 29:5279–5285CrossRef Cai X, Zhang JL, Ouyang Y, Ma D, Tan SZ, Peng YL (2013) Bacteria-adsorbed palygorskite stabilizes the quaternary phosphonium salt with specific-targeting capability, long-term antibacterial activity and lower cytotoxicity. Langmuir 29:5279–5285CrossRef
30.
go back to reference Cai X, Lin MS, Tan SZ, Mai WJ, Zhang YM, Liang ZW, Lin ZD, Zhang XJ (2012) The use of polyethyleneimine-modified reduced graphene oxide as a substrate for silver nanoparticles to produce a material with lower cytotoxicity and long-term antibacterial activity. Carbon 50:3407–3415CrossRef Cai X, Lin MS, Tan SZ, Mai WJ, Zhang YM, Liang ZW, Lin ZD, Zhang XJ (2012) The use of polyethyleneimine-modified reduced graphene oxide as a substrate for silver nanoparticles to produce a material with lower cytotoxicity and long-term antibacterial activity. Carbon 50:3407–3415CrossRef
31.
go back to reference Cai X, Dai GJ, Tan SZ, Ouyang Y, Ouyang YS, Shi QS (2012) Synergistic antibacterial zinc ions and cerium ions loaded α-zirconium phosphate. Mater Lett 67:199–201CrossRef Cai X, Dai GJ, Tan SZ, Ouyang Y, Ouyang YS, Shi QS (2012) Synergistic antibacterial zinc ions and cerium ions loaded α-zirconium phosphate. Mater Lett 67:199–201CrossRef
32.
go back to reference Wu T, Xie AG, Tan SZ, Cai X (2011) Antimicrobial effects of quaternary phosphonium salt intercalated clay minerals on Escherichia coli and Staphylococci aureus. Colloid Surf B 86:232–236CrossRef Wu T, Xie AG, Tan SZ, Cai X (2011) Antimicrobial effects of quaternary phosphonium salt intercalated clay minerals on Escherichia coli and Staphylococci aureus. Colloid Surf B 86:232–236CrossRef
33.
go back to reference Cai X, Tan SZ, Yu AL, Zhang JL, Liu JH, Mai WJ, Jiang ZY (2012) Sodium 1-naphthalenesulfonate-functioned reduced graphene oxide stabilize the silver nanoparticles with lower cytotoxicity and long-term antibacterial activity. Chem-Asian J 7:1664–1670CrossRef Cai X, Tan SZ, Yu AL, Zhang JL, Liu JH, Mai WJ, Jiang ZY (2012) Sodium 1-naphthalenesulfonate-functioned reduced graphene oxide stabilize the silver nanoparticles with lower cytotoxicity and long-term antibacterial activity. Chem-Asian J 7:1664–1670CrossRef
34.
go back to reference Cai X, Tan SZ, Lin MS, Xie AG, Mai WJ, Zhang XJ, Lin ZD, Wu T, Liu YL (2011) Synergistic antibacterial brilliant blue/reduced graphene oxide/quaternary phosphonium salt composite with excellent water-solubility and specific-targeting capability. Langmuir 27:7828–7835CrossRef Cai X, Tan SZ, Lin MS, Xie AG, Mai WJ, Zhang XJ, Lin ZD, Wu T, Liu YL (2011) Synergistic antibacterial brilliant blue/reduced graphene oxide/quaternary phosphonium salt composite with excellent water-solubility and specific-targeting capability. Langmuir 27:7828–7835CrossRef
35.
go back to reference Li M, Zhou X, Zeng X, Wang C, Xu J, Ma D, Xue W (2016) Folate-targeting redox hyperbranched poly(amido amine)s delivering MMP-9 siRNA for cancer therapy. J Mater Chem B 4:547–556CrossRef Li M, Zhou X, Zeng X, Wang C, Xu J, Ma D, Xue W (2016) Folate-targeting redox hyperbranched poly(amido amine)s delivering MMP-9 siRNA for cancer therapy. J Mater Chem B 4:547–556CrossRef
36.
go back to reference Zhou X, Zheng Q, Wang C, Xu J, Wu JP, Kirk TB, Ma D, Xue W (2016) Star-shaped amphiphilic hyperbranched polyglycerol conjugated with dendritic poly(L-lysine) for the codelivery of docetaxel and MMP-9 siRNA in cancer therapy. ACS Appl Mater Interfaces 8:12609–12619CrossRef Zhou X, Zheng Q, Wang C, Xu J, Wu JP, Kirk TB, Ma D, Xue W (2016) Star-shaped amphiphilic hyperbranched polyglycerol conjugated with dendritic poly(L-lysine) for the codelivery of docetaxel and MMP-9 siRNA in cancer therapy. ACS Appl Mater Interfaces 8:12609–12619CrossRef
Metadata
Title
Genipin cross-linked chitosan hydrogel for the controlled release of tetracycline with controlled release property, lower cytotoxicity, and long-term bioactivity
Authors
Wu Zhang
Guangli Ren
Hao Xu
Jinglin Zhang
Huidi Liu
Shansong Mu
Xiang Cai
Ting Wu
Publication date
01-08-2016
Publisher
Springer Netherlands
Published in
Journal of Polymer Research / Issue 8/2016
Print ISSN: 1022-9760
Electronic ISSN: 1572-8935
DOI
https://doi.org/10.1007/s10965-016-1059-5

Other articles of this Issue 8/2016

Journal of Polymer Research 8/2016 Go to the issue

Premium Partners