Chitosan/ Alginate /Gellan Gum Hybrid Hydrogel as a Vehicle for Controlled Release of Drug
International Journal of Biomedical Materials Research
Volume 7, Issue 1, June 2019, Pages: 16-23
Received: Jan. 16, 2019; Accepted: Feb. 20, 2019; Published: Mar. 6, 2019
Views 657      Downloads 112
Jiunn-An Pan, Graduate Institution Engineering Technology-Doctoral, National Taipei University of Technology, Taipei, Taiwan; New Taipei Municipal Yonghe Junior High School, New Taipei City, Taiwan
Hsuan-Liang Liu, Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, Taiwan
Ko-Shao Chen, Department of Materials Engineering, Tatung University, Taipei, Taiwan
Article Tools
Follow on us
Hybrid hydrogel was fabricated by a classic sol-gel method using EDC/NHS as crosslink reagent grafting onto the thermoplastic polyurethane (TPU), nonwoven fabric, for controlled release of drug. In this study, precursor acetic acid (AA) was used to plasma deposit on the surface of TPU to form a hydrophilic thin film. Hybrid hydrogel was investigated through scanning electron microscopy (SEM), water contact angle (WCA) measurement, Fourier transform infra-red (FTIR) spectroscopy, UV/V is spectroscopy, equilibrium swelling ratio, MTT assay and drug delivery system studies. This polyelectrolyte complexes (PECs) formed hydrogel, pH-sensitive type, was evaluated at pH value of 1.2 and 7.4 of buffer solution and at temperature of 37C to observe its rate of swelling and drug release features with caffeine. Moreover, the mechanism of caffeine release from membrane devices (n=0.58) are anomalous transport, non-Fickian diffusion, the value of n lies between 0.43 and 0.85. It has an excellent release ratio up to about 90% absorption cumulative amounts of caffeine at pH 7.4 after 8h and could be a beneficial carrier for fragile drugs.
TPU, Acetic Acid Plasma, EDC/NHS Grafting, Hybrid Hydrogel
To cite this article
Jiunn-An Pan, Hsuan-Liang Liu, Ko-Shao Chen, Chitosan/ Alginate /Gellan Gum Hybrid Hydrogel as a Vehicle for Controlled Release of Drug, International Journal of Biomedical Materials Research. Vol. 7, No. 1, 2019, pp. 16-23. doi: 10.11648/j.ijbmr.20190701.13
Copyright © 2019 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Qi-Wei Lu and Christopher W. Macosko. Promoting Adhesion to Thermoplastic Polyurethane (TPU) by Amine Functional Polypropylenes. Polymeric Materials: Science & Engineering 2003; 89:844-7.
Emre Basturk, Serfullas Madakbas, Memet Vezir Kahraman. Improved Thermal Stability and Wettability Behavior of Thermoplastic Polyurethane/Barium Metaborate Composites. Materials Research 2016; 19:434-9.
A. Boubakri, N. Guermazi, K. Elleuch, et al. Study UV-aging of thermoplastic polyurethane material. Materials Science and Engineering A 2010; 527:1649-54.
Y. Jia, Z. Jiang, X. L. Gong, et al. Creep of thermoplastic polyurethane reinforced with ozone functionalized Carbon nanotubes. eXPRESS Polymer Letters 2012 ; 6:750-8.
Katsuji Matsunaga, Kyoko Sato, Masahiro Tajima, et al. Gas Permeability of Thermoplastic Polyurethane Elastomers. Polymer Journal 2005; 37:413-7.
E. L. Larionova, T. N. Kalinina, T. I. Chufarovskaya, et al. Fibre, Film, and Porous Materials Based on Chitosan. Fibre Chemistry 1995; 27:392-6.
Sunil A. Aginhotri, Nadagouda N. Mallikarjana, Tejraj M. Aminabhavi. Recent advances on chitosan-based micro-and nanoparticles in drug delivery. Journal of Controlled Release 2004; 100:5-28.
S. Demarger-Andre & A. Domard. Chitosan carboxylic acid salts in solution and in solid state. Carbohydrate Polymer 1994; 23 :211-9.
Sang Yond Nam, Young Moo Lee. Pervaporation and properties of chitosan-poly (acrylic acid) complex membranes. Journal of membrane science 1997; 135:161-71.
M. V. Shamov, S. Yu. Bratskyaya, and V. A. Avoramenko. Interaction of Carboxylic acid with Chitosan: Effect of pK and Hydrocarbon Chain Length. Journal of Colloid and Interface Science 2002; 249:316-21.
Majeti N. V., Ravi Kumar. A review of chitin and chitosan applications. Reactive & Functional Polymers 2000; 46:1-27.
Narimane Mati-Baynast, Pierre-Henri Elchingeer, Helenede Baynast, et al. Chitosan as an adhesive. European Polymer Journal 2014; 60:198-212.
J. Berger, M. Reist, J. M. Mayer, et al. Structure and interaction in chitosan hydrogels formed by complexation or aggregation for biomedical applications. European Journal of Pharmaceutics and Biopharmaceutics 2004; 57:35-52.
George Pasparakis, Nikolaos Bouropoulos. Swelling studies and in vitro release of verapamil from calcium alginate and calcium alginate-chitosan beads. International Journal of Pharmaceutics 2006; 323:34-42.
Cornelus G. de Kruif, Fanny Weinbreck, Renko de Vries. Complex coacervation of proteins and anionic polysaccharides. Current Opinion in Colloid & Interface Science 2004; 9:340-9.
Meera George, T. Emilia Abraham, Polyionic hydrocolloids for the intestinal delivery of protein drug: Alginate and chitosan – a review. Journal of controlled release 2006; 114:1-14.
Carolina Siqueira Franco Picone, Rosiane Lopes Cunha. Chitosan-gellan electrostatic complexes: Influence of preparation conditions and surfactant presence. Carbohydrate Polymers 2013; 94:695-703.
Felix N. A. Aryee, Michael T. Nickerson. Effect of pH, biopolymer mixing ratio and salts on the formation and stability of electrostatic complexes formed within mixtures of lentil protein isolate and anionic polysaccharides (κ-carrageen and gellan gum). International Journal of Food Science and Technology 2014; 49:65-71.
Wayne R. Gombotz, Siow Fong Wee. Protein release from alginate matrices. Advanced Drug Delivery Reviews 2012; 64:194-205.
B. Thu, P. Bruheim, T. Espevik, et al. Alginate polycation microcapsules Ⅰ. Interaction between alginate and polycation, Biomaterials1996; 17:1031-40.
Hucheng Zhang, Honghe Zheng, Qingzhi Zhang, et al. The Interaction of Sodium Alginate with Univalent Cation, Biopolymers 1998; 46:395-402.
Kuen Yong Lee, David J. Moonney. Alginate: Properties and biomedical applications. Progress in Polymer Science 2012; 37:106-26.
Qiang Qian, Walter Bonani, Devid Maniglio, Jie Chen, Claudio Migliaresi, Modulating the release of drugs from alginate matrices with the addition of gelatin microbeads, Journal of Bioactive and Compatible, Polymers, 2014; 29:193-207.
Per-Erik Jansson, Bengt Lindberg. Structural Studies of Gellan Gum, An Extracellular Polysaccharide Elaborated By Pseudomonas elodea. Carbohydrate Research 1983; 124:135-9.
Cameron John Ferris and Marcinhet Panhuis. Conducting bio-materials based on gellan gum hydrogels. Soft Matter 2009; 5:3430-37.
F. Yamamoto, R. L. Cunha, Acid gelation of gellan:Effect of final pH and heat treatment conditions, Carbohydrate Polymers 2007; 68:517-27.
Edwin R. Morris, Katsuyoshi Nishinari, Marguerite Rinaudo, Gelation of gellan – A review 2012; 28:373-411.
Stefan kasapis, Persephoni Giannouli, Miles W. N. Hember, et al. Structure aspects and phase behavior in deacylated and high acyl gellan systems, Carbohydrate Polymers 1999; 38:145-54.
Emako Miyoshi, Tomohisa Takaya & Katsuyoshi Nishinari. Rheological and thermal studies of gel-sol transition ingellan gum aqueous solutions, Carbohydrate Polymers 1996; 30: 109-19.
Yangchao Luo, Qin Wang. Recent development of chitosan-based polyelectrolyte complexes with natural polysaccharides for drug delivery, International Journal of Biological Macromolecules 2014; 64:353-67.
Brahma N. Singh, Kwon H. Kim. Effects of divalent cations on drug encapsulation efficiency of deacylated gellan gum, Journal of Microencapsulation 2005; 22:761-71.
Giorgia DˊArrigo, Gemma Navarro, Chiara Di Meo, et al. Gellan gum nanohydrogel containing antiflammatory and anti-cancer drugs: a multi-drug delivery system for a combination therapy in cancer treatment. European Journal of Pharmaceutics and Biopharmaceutics 2014; 87:208-16.
Mrunalini Narkar, Praveen Sher, and Atmaram Pawar, Stomach-Specific Controlled Release Gellan Beads of Acid-Soluble Drug Prepared by Ionotropic Gelation Method, AAPS PharmSciTech 2010; 11:267-77.
Mohammed Reza Amiryousefi, Mohebbat Mohebbi, Shiva Golmohammadzadeh et al. Encapsulation of caffeine in hydrogel colloidosome: optimization of fabrication, characterization and release kinetics evaluation. Flavour and Fragrance Journal 2016; 31:163-72.
Aleksandra Szopa, Ewa Poleszak, Elzbieta Wyska, et al. Caffeine enhances the antipressant-like activity of common antidepressant drugs in the forced swim test in mice, Maunyn-Schmiedebergˊs Arch Pharmacol., 2016; 389:211-21.
Puncan Turnbull, Joseph V. Rodricks, Gregory F. Mariano. Neurobehavioral hazard identification and characterization for caffeine. Regulatory Toxicology and Pharmacology 2016; 74:81-92.
James G. Phillips, Jonathan Currie, and Rowan P. Ogeil. Consumption and foraging behavior for common stimulants (nicotine, caffeine) , Journal of Addictive Diseases 2016; 35: 15-21.
Giuseppe Grosso, Agnieszka Pajak and Fabio Galvano, Coffee, tea, caffeine and risk of depression: A systematic review and observational studies. Mol. Nutr. Food Res. 2016; 60: 223-34.
J. M. Goddard, J. H. Hotchkiss. Polymer surface modification for the attachment of bioactive compounds. Progress in Polymer Science 2007; 32:698-725.
L. Bardos, H. Barankova. Cold atmospheric plasma: Sources, processes and applications. Thin Solid Films 2010; 518:6705-13.
H. Yasuda and M. Gazicki. Biomedical applicatiohs of plasma polymerization and plasma treatment of polymer surfaces. Biomaterials 1982; 3:69-77.
K. S. Chen, T. S. Hung, H. M. Wu, et al. Preparation thermosensitive gold nanoparticles by plasma pretreatment and UV grafted polymerization. Thin Solid Films 2010; 518:7568-37.
Jianping Deng, Lifu Wang, Lianying Liu, et al. Developments and new applications of UV-induced surface draft polymerizations. Progress in Polymer Science 2009; 34:156-93.
Dave Mangindaan, Wei-Hsuan Kuo, Ching-Chuan Chang, et al. Plasma polymerization of amine-containing thin films and the studies on the deposition kinetics. Surface & Coatings Technology 2011; 206:1299-1306.
Annemie Bogaerts, Erik Neyts, Renaat Gijbels, et al. Gas discharge plasma and their applications Spectrochimica Acta Part B 2002; 57:609-18.
M. Morra, E. Occhiello, and F. Garbassi, Contact Angle Hysteresis on Oxgen Plasma Treated Polypropylene Surfaces, Journal of Colloid Interface Science 1989; 132:504-8.
Jay J. Senkevich, Oxidation chemical vapor deposition of polyacenaphthylene, polyacenaphthylene and polyindane via benzoyl peroxide, Thin Solid Films 2014; 556:23-7.
Naohisa Akashi, Shin-ichi Kuroda, Protein immobilization onto poly (vinylidene fluoride) microporous membranes active by the atmospheric pressure low temperature plasma, Polymer 2014; 55:2780-91.
Yashao Chen, Qiang Gao, Haiyan Wan, et al. Surface modification and biocompatible improvement of polystyrene film by Ar, O2 and Ar + O2 plasma. Applied Surface Science 2013; 265:452-7.
M. Garcia-Vargas, C. Gonzales-Chomon, B. Magarinos, A. Concheiro, C. Alvarez-Lorenzo, E. Bucio, Acrylic polymer-grafted polypropylene sutures for covalent immobilization or reversible adsorption of vancomycin, International Journal of Pharmaceutics 2014; 461:286-95.
Yun Zhao, Alberto Fina, Alberto Venturello, et al. Effect of gas atmospheres on poly (lactic acid) films in acrylic acid plasma treatment. Applied Surface Science 2013; 283:181-7.
Ko-Shao Chen, Yuan-An Ku, Chi-Han Lee, Hong-Ru Lin, Feng-Huei Lin, Tim-Mo Chem, Immobilization of chitosan gel with cross-linking reagent on PNIPAAm gel/PP nonwoven composites surface, Materials Science and Engineering C 2010; 25:472-8.
Suseen Jayachandran, Annelies Delabie, Jens Maggen, et al. Chemical vapor deposition processes for the fabrication of epitaxial Si-O superlattices. Thin Solid Films 2014; 557:36-41.
Pietro Matricardi, Claudia Cencetti, Roberto Ria, et al. Preparation and Characterization of Novel Gellan Gum Hydrogels Suitable for Modified Drug Release. Molecules 2009; 14:3376-91.
Yan Xiao, Xiaohua Zhou. Synthesis and properties of a novel crosslinked chitosan resin modified by L-lysine. Reactive & Functional Polymers 2008; 68:1281-9.
Ganesan Krishnamoorthy, Praveen Kumar Sehgal, Asit Baran Mandal, et al. Novel collagen scaffolds prepared by using unnatural D-amino acid assisted EDC/NHS crosslinking. Journal of Biomaterials Science 2013; 24:344-64.
Chunrong Yang. Enhance physicochemical properties of collagen by using EDC/NHS-crosslinking. Bull. Mater. Sci. 2012; 35:913-8.
J. M. Goddard, J. H. Hotchkiss. Polymer surface modification for the attachment of bioactive compounds. Progress in Polymer Science 2007; 32:698-725.
Vartika Dhyani and Neetu Sigh. Controlling the Cell Adhesion Property of Silk Films by Graft Polymerization. ACS Appl. Mater. Interfaces 2014; 6:5005-11.
William E. Price, Kirsten A. Trickett and Kenneth R. Harris. Association of Caffeine in Aqueous Solution. J. Chem. Soc., Faraday Trans. 1 1989: 85, 3281-8.
Science Publishing Group
1 Rockefeller Plaza,
10th and 11th Floors,
New York, NY 10020
Tel: (001)347-983-5186