Glutathione-Responsive Carboxymethyl Chitosan Nanoparticles for Controlled Release of Herbicides


Glutathione-responsive carboxymethyl chitosan nanoparticles cross-linked with disulfide bonds were developed for controlled release of herbicides. The nanoparticles were synthesized by selfassembly of amphiphilic carboxymethyl chitosan derivative (CMCS-MUA) in aqueous solution and subsequently producing disulfide cross-linking bonds by ultrasonic treatment. TEM showed that the nanoparticles had a spherical core-shell configuration with a size of about 250 nm. Assessment of stability of the nanoparticles (considering mean diameter, polydispersity, and Zeta potential) was conducted over a period of three months, and the nanoparticles were found to be stable in solution. Herbicide-loaded nanoparticles were prepared using diuron as a model herbicide. In vitro release study revealed that diuron can be released from nanoparticles in a controlled manner depended on the glutathione concentration. Herbicidal activity assays performed with preemergence treatment of target species (Echinochloa crusgalli) showed the effectiveness of diuron- loaded nanoparticles. Assays with nontarget species (Zea mays) showed that the diuronloaded nanoparticles did not affect plant growth. The results indicate that the glutathioneresponsive nanoparticles prepared in this work will be a promising candidate for controlled release of herbicides in agriculture.

Share and Cite:

Yu, Z. , Sun, X. , Song, H. , Wang, W. , Ye, Z. , Shi, L. and Ding, K. (2015) Glutathione-Responsive Carboxymethyl Chitosan Nanoparticles for Controlled Release of Herbicides. Materials Sciences and Applications, 6, 591-604. doi: 10.4236/msa.2015.66062.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Cotterill, J.V., Wilkins, R.M. and da Silva, F.T. (1996) Controlled Release of Diuron Granules Based on a Lignin Matrix System. Journal of Controlled Release, 40, 133-142.
[2] Fernandez-Perez, M., Villafranca-Sanchez, M., Gonzalez-Pradas, E. and Flores-Cespedes, F. (1999) Controlled Release of Diuron from an Alginate-Bentonite Formulation: Water release Kinetics and Soil Mobility Study. Journal of Agricultural and Food Chemistry, 47, 791-798.
[3] Agnihotri, S.A. and Aminabhavi, T.M. (2004) Controlled Release of Clozapine through Chitosan Microparticles Prepared by a Novel Method. Journal of Controlled Release, 96, 245-259.
[4] Grillo, R., Pereira Anderson do Espirito, S., de Melo Nathalie Ferreira, S., Porto Raquel, M., Feitosa Leandro, O., Tonello Paulo, S., et al. (2011) Controlled Release System for Ametryn Using Polymer Microspheres: Preparation, Characterization and Release Kinetics in Water. Journal of Hazardous Materials, 186, 1645-1651.
[5] Grillo, R., dos Santos Nathalia Zocal, P., Maruyama Cintia, R., Rosa Andre, H., de Lima, R. and Fraceto Leonardo, F. (2012) Poly(ε-caprolactone) Nanocapsules as Carrier Systems for Herbicides: Physico-Chemical Characterization and Genotoxicity Evaluation. Journal of Hazardous Materials, 231-232, 1-9.
[6] Roy, A., Singh, S.K., Bajpai, J. and Bajpai, A.K. (2014) Controlled Pesticide Release from Biodegradable Polymers. Central European Journal of Chemistry, 12, 453-469.
[7] Riggle, B.D. and Penner, D. (1990) The Use of Controlled-Release Technology for Herbicides. Reviews of Weed Science, 5, 1-14.
[8] Yu-Ling, L., Li, Z., Zhaozhong, L., Ru, C., Fenghua, M., Jing-Hao, C., et al. (2009) Reversibly Stabilized Multifunctional Dextran Nanoparticles Efficiently Deliver Doxorubicin into the Nuclei of Cancer Cells. Angewandte Chemie, International Edition, 48, 9914-9918.
[9] Tian-Bin, R., Yue, F., Zhong-Hai, Z., Lan, L. and Yong-Yong, L. (2011) Shell-Sheddable Micelles Based on Star- Shaped Poly(ε-caprolactone)-SS-poly(ethyl glycol) Copolymer for Intracellular Drug Release. Soft Matter, 7, 2329- 2331.
[10] Russo, A., DeGraff, W., Friedman, N. and Mitchell, J.B. (1986) Selective Modulation of Glutathione Levels in Human Normal versus Tumor Cells and Subsequent Differential Response to Chemotherapy Drugs. Cancer Research, 46, 2845-2848.
[11] Arrick, B.A. and Nathan, C.F. (1984) Glutathione Metabolism as a Determinant of Therapeutic Efficacy: A Review. Cancer Research, 44, 4224-4232.
[12] Schafer, F.Q. and Buettner, G.R. (2001) Redox Environment of the Cell as Viewed through the Redox State of the Glutathione Disulfide/Glutathione Couple. Free Radical Biology & Medicine, 30, 1191-1212.
[13] Ojima, I. (2008) Guided Molecular Missiles for Tumor-Targeting Chemotherapy—Case Studies Using the Second- Generation Taxoids as Warheads. Accounts of Chemical Research, 41, 108-119.
[14] Bauhuber, S., Hozsa, C., Breunig, M. and Goepferich, A. (2009) Delivery of Nucleic Acids via Disulfide-Based Carrier Systems. Advanced Materials, 21, 3286-3306.
[15] Ball, L.A., Gian, P., Bechtold, U., Creissen, G., Funck, D., Jimenez, A., et al. (2004) Evidence for a Direct Link between Glutathione Biosynthesis and Stress Defense Gene Expression in Arabidopsis. The Plant Cell, 16, 2448-2462.
[16] Yin, Y.H., Lv, X.L., Tu, H.W., Xu, S. and Zheng, H. (2010) Preparation and Swelling Kinetics of pH-Sensitive Photocrosslinked Hydrogel Based on Carboxymethyl Chitosan. Journal of Polymer Research, 17, 471-479.
[17] Upadhyaya, L., Singh, J., Agarwal, V. and Tewari, R.P. (2013) Biomedical Applications of Carboxymethyl Chitosans. Carbohydrate Polymers, 91, 452-466.
[18] Liu, X.F., Guan, Y.L., Yang, D.Z., Li, Z. and Yao, K.D. (2001) Antibacterial Action of Chitosan and Carboxymethylated Chitosan. Journal of Applied Polymer Science, 79, 1324-1335.<1324::AID-APP210>3.0.CO;2-L
[19] Anitha, A., Divya Rani, V.V., Krishna, R., Sreeja, V., Selvamurugan, N., Nair, S.V., et al. (2009) Synthesis, Characterization, Cytotoxicity and Antibacterial Studies of Chitosan, O-Carboxymethyl and N,O-Carboxymethyl Chitosan Nanoparticles. Carbohydrate Polymers, 78, 672-677.
[20] Chen, X.G. and Park, H.J. (2003) Chemical Characteristics of O-Carboxymethyl Chitosans Related to the Preparation Conditions. Carbohydrate Polymers, 53, 355-359.
[21] Gao, C., Liu, T., Dang, Y.H., Yu, Z.Y., Wang, W., Guo, J.J., et al. (2014) pH/Redox Responsive Core Cross-Linked Nanoparticles from Thiolated Carboxymethyl Chitosan for in Vitro Release Study of Methotrexate. Carbohydrate Polymers, 111, 964-970.
[22] Perera, G., Barthelmes, J. and Bernkop-Schnuerch, A. (2010) Novel Pectin-4-Aminothiophenole Conjugate Microparticles for Colon-Specific Drug Delivery. Journal of Controlled Release, 145, 240-246.
[23] Kurkdjian, A. and Guern, J. (1989) Intracellular pH: Measurement and Importance in Cell Activity. Annual Review of Plant Physiology and Plant Molecular Biology, 40, 271-303.
[24] Pereira, A.E.S., Grillo, R., Mello, N.F.S., Rosa, A.H. and Fraceto, L.F. (2014) Application of Poly(Epsilon-Caprolac- tone) Nanoparticles Containing Atrazine Herbicide as an Alternative Technique to Control Weeds and Reduce Damage to the Environment. Journal of Hazardous Materials, 268, 207-215.
[25] Grillo, R., Pereira, A.E.S., Nishisaka, C.S., de Lima, R., Oehlke, K., Greiner, R., et al. (2014) Chitosan/Tripolyphos- phate Nanoparticles Loaded with Paraquat Herbicide: An Environmentally Safer Alternative for Weed Control. Journal of Hazardous Materials, 278, 163-171.
[26] Garcia, R., Jose L., Parra, A. and Aleman, J. (2008) Efficient Synthesis of Disulfides by Air Oxidation of Thiols under Sonication. Green Chemistry, 10, 706-711.
[27] Chang, D., Lei, J., Cui, H.R., Lu, N., Sun, Y.J., Zhang, X.H., Gao, C., Zheng, H. and Yin, Y.H. (2012) Disulfide Cross-Linked Nanospheres from Sodium Alginate Derivative for Inflammatory Bowel Disease: Preparation, Characterization, and in Vitro Drug Release Behavior. Carbohydrate Polymers, 88, 663-669.
[28] Hua, S.B. and Wang, A.Q. (2009) Synthesis, Characterization and Swelling Behaviors of Sodium Alginate-g-Poly (Acrylic Acid)/Sodium Humate Superabsorbent. Carbohydrate Polymers, 75, 79-84.
[29] Pourjavadi, A., Sadeghi, M. and Hosseinzadeh, H. (2004) Preparation, Swelling Behavior, Salt- and pH-Sensitivity of Partially Hydrolyzed Crosslinked Carrageenan-Graft-Polymethacrylamide Superabsorbent Hydrogel. Polymers for Advanced Technologies, 15, 645-653.
[30] Liu, K.-H., Chen, B.-R., Chen, S.-Y. and Liu, D.-M. (2009) Self-Assembly Behavior and Doxorubicin-Loading Capacity of Acylated Carboxymethyl Chitosans. The Journal of Physical Chemistry B, 113, 11800-11807.
[31] Liu, T.-Y., Chen, S.-Y., Lin, Y.-L. and Liu, D.-M. (2006) Synthesis and Characterization of Amphiphatic Carboxymethyl-Hexanoyl Chitosan Hydrogel: Water-Retention Ability and Drug Encapsulation. Langmuir, 22, 9740-9745.
[32] Cheng, R., Feng, F., Meng, F., Deng, C., Feijen, J. and Zhong, Z. (2014) Glutathione-Responsive Nano-Vehicles as a Promising Platform for Targeted Intracellular Drug and Gene Delivery. Journal of Controlled Release, 152, 2-12.
[33] Yang, D., Chen, W.L. and Hu, J.H. (2014) Design of Controlled Drug Delivery System Based on Disulfide Cleavage Trigger. The Journal of Physical Chemistry B, 118, 12311-12317.
[34] Meng, F.H., Hennink, W.E. and Zhong, Z.Y. (2009) Reduction-Sensitive Polymers and Bioconjugates for Biomedical Applications. Biomaterials, 30, 2180-2198.
[35] Barrett, M. (1995) Metabolism of Herbicides by Cytochrome P450 in Corn. Drug Metabolism and Drug Interactions, 12, 299-315.
[36] Barrett, M. (1997) Herbicide Selectivity Mechanisms in Maize: Using What We Know for the Future. Brighton Crop Protection Conference-Weeds, 2, 587-596.
[37] de Oliveira, J.L., Vangelie Ramos Campos, E., da Silva, C.M.G., Pasquoto, T., Lima, R. and Fraceto, L.F. (2015) Solid Lipid Nanoparticles Co-Loaded with Simazine and Atrazine: Preparation, Characterization, and Evaluation of Herbicidal Activity. Journal of Agricultural and Food Chemistry, 63, 422-432.

Copyright © 2022 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.