This study was carried out to prepare ZnO nanoparticles incorporated acrylamide grafted chitosan composite film for possible biomedical application especially drug loading in wound healing. ZnO nanoparticles were prepared by co-precipitation method from zinc acetate di-hydrate and incorporated in acrylamide grafted chitosan. FT-IR and TGA of the prepared composite film confirmed the successful incorporation of ZnO nanoparticles in the acrylamide-grafted polymer matrix. SEM images showed that the ZnO nanoparticles were homogeneously distributed on the porous matrix of the composite film. Water uptake and buffer uptake analysis revealed that the composite film could hold water and buffer sufficiently, which facilitated the absorption of exudate from the wound site. Amoxicillin was loaded in the prepared composite film and the maximum loading efficiency was found to be 67.33% with drug concentration of 300 ppm. In vitro studies showed greater antimicrobial activity of drug-loaded composite film compared to both pure film and standard antibiotic disc. Finally, the In vivo mouse model showed maximum healing efficiency compared to conventional gauge bandages because the loading of antibiotic in the film produced a synergistic effect and healing time was reduced.
References
[1]
Anisuzzaman, D., et al. (2022) Wound Severity Classification Using Deep Neural Network. arXiv: 2204.07942.
[2]
Rothe, M. and Falanga, V. (1989) Growth Factors: Their Biology and Promise in Dermatologic Diseases and Tissue Repair. Archives of Dermatology, 125, 1390-1398. https://doi.org/10.1001/archderm.1989.01670220086015
[3]
Shakespeare, P. (2001) Burn Wound Healing and Skin Substitutes. Burns, 27, 517-522. https://doi.org/10.1016/S0305-4179(01)00017-1
[4]
Boateng, J. and Catanzano, O. (2015) Advanced Therapeutic Dressings for Effective Wound Healing—A Review. Journal of Pharmaceutical Sciences, 104, 3653-3680. https://doi.org/10.1002/jps.24610
[5]
Karumathil, D.P., Surendran-Nair, M. and Venkitanarayanan, K. (2016) Efficacy of Trans-Cinnamaldehyde and Eugenol in Reducing Acinetobacter Baumannii Adhesion to and Invasion of Human Keratinocytes and Controlling Wound Infection in Vitro. Phytotherapy Research, 30, 2053-2059. https://doi.org/10.1002/ptr.5713
[6]
Peppas, N.A. and Buri, P.A. (1985) Surface, Interfacial and Molecular Aspects of Polymer Bioadhesion on Soft Tissues. Journal of Controlled Release, 2, 257-275. https://doi.org/10.1016/0168-3659(85)90050-1
[7]
Date, A.A., Hanes, J. and Ensign, L.M. (2016) Nanoparticles for Oral Delivery: Design, Evaluation and State-of-the-Art. Journal of Controlled Release, 240, 504-526. https://doi.org/10.1016/j.jconrel.2016.06.016
[8]
Casettari, L., et al. (2012)PEGylated Chitosan Derivatives: Synthesis, Characterizations and Pharmaceutical Applications. Progress in Polymer Science, 37, 659-685. https://doi.org/10.1016/j.progpolymsci.2011.10.001
[9]
Younes, I. and Rinaudo, M. (2015) Chitin and Chitosan Preparation from Marine Sources. Structure, Properties and Applications. Marine Drugs, 13, 1133-1174. https://doi.org/10.3390/md13031133
[10]
Pokhrel, S., Yadav, P.N. and Adhikari, R. (2015) Applications of Chitin and Chitosan in Industry and Medical Science: A Review. Nepal Journal of Science and Technology, 16, 99-104. https://doi.org/10.3126/njst.v16i1.14363
[11]
Hao, R., et al. (2018) Superior Potassium Storage in Chitin-Derived Natural Nitrogen-Doped Carbon Nanofibers. Carbon, 128, 224-230. https://doi.org/10.1016/j.carbon.2017.11.064
[12]
Hamedi, H., Moradi, S., Hudson, S.M. and Tonelli, A.E.(2018)Chitosan Based Hydrogels and Their Applications for Drug Delivery in Wound Dressings: A Review. Carbohydrate Polymers, 199, 445-460. https://doi.org/10.1016/j.carbpol.2018.06.114
[13]
Mima, S., Miya, M., Iwamoto, R. and Yoshikawa, S.(1983)Highly Deacetylated Chitosan and Its Properties. Journal of Applied Polymer Science, 28, 1909-1917. https://doi.org/10.1002/app.1983.070280607
[14]
Li, C., Han, Q.Y., Guan, Y. and Zhang, Y.J.(2015)Michael Reaction of Chitosan with Acrylamides in an Aqueous Alkali-Urea Solution. Polymer Bulletin, 72, 2075-2087. https://doi.org/10.1007/s00289-015-1390-8
[15]
Xie, W., Xu, P. and Liu, Q. (2001) Antioxidant Activity of Water-Soluble Chitosan Derivatives. Bioorganic & Medicinal Chemistry Letters, 11, 1699-1701. https://doi.org/10.1016/S0960-894X(01)00285-2
[16]
Xie, W., Xu, P.X., Wang, W. and Liu, Q.(2002)Preparation and Antibacterial Activity of a Water-Soluble Chitosan Derivative. Carbohydrate Polymers, 50, 35-40. https://doi.org/10.1016/S0144-8617(01)00370-8
[17]
Alves, N.M. and Mano, J.F. (2008) Chitosan Derivatives Obtained by Chemical Modifications for Biomedical and Environmental Applications. International Journal of Biological Macromolecules, 43, 401-414. https://doi.org/10.1016/j.ijbiomac.2008.09.007
[18]
Mather, B.D., Viswanathan, K., Miller, K.M. and Long, T.E.(2006)Michael Addition Reactions in Macromolecular Design for Emerging Technologies. Progress in Polymer Science, 31, 487-531. https://doi.org/10.1016/j.progpolymsci.2006.03.001
[19]
Bulut, E. and Turhan, Y. (2021) Synthesis and Characterization of Temperature-Sensitive Microspheres Based on Acrylamide Grafted Hydroxypropyl Cellulose and Chitosan for the Controlled Release of Amoxicillin Trihydrate. International Journal of Biological Macromolecules, 191, 1191-1203. https://doi.org/10.1016/j.ijbiomac.2021.09.193
[20]
Salehi, R., et al. (2010)Novel Biocompatible Composite (Chitosan-Zinc Oxide Nanoparticle): Preparation, Characterization and Dye Adsorption Properties. Colloids and Surfaces B: Biointerfaces, 80, 86-93. https://doi.org/10.1016/j.colsurfb.2010.05.039
[21]
Yan, E., et al. (2011)Synthesis and Characterization of Fluorescent Chitosan-ZnO Hybrid Nanospheres. Materials Science and Engineering: B, 176, 458-461. https://doi.org/10.1016/j.mseb.2011.01.005
[22]
Cai, J. and Zhang, L. (2005) Rapid Dissolution of Cellulose in LiOH/Urea and NaOH/Urea Aqueous Solutions. Macromolecular Bioscience, 5, 539-548. https://doi.org/10.1002/mabi.200400222
[23]
Cai, J. and Zhang, L. (2006) Unique Gelation Behavior of Cellulose in NaOH/Urea Aqueous Solution. Biomacromolecules, 7, 183-189. https://doi.org/10.1021/bm0505585
[24]
Rashid, T.U., et al. (2012)A New Approach for The Preparation of Chitosan from γ-Irradiation of Prawn Shell: Effects of Radiation on the Characteristics of Chitosan. Polymer International, 61, 1302-1308. https://doi.org/10.1002/pi.4207
[25]
Chen, C., Liu, P. and Lu, C. (2008) Synthesis and Characterization of Nano-Sized ZnO Powders by Direct Precipitation Method. Chemical Engineering Journal, 144, 509-513. https://doi.org/10.1016/j.cej.2008.07.047
[26]
Sashiwa, H., et al. (2003)Michael Reaction of Chitosan with Various Acryl Reagents in Water. Biomacromolecules, 4, 1250-1254. https://doi.org/10.1021/bm030022o
[27]
Dai, M., et al. (2009)Chitosan-Alginate Sponge: Preparation and Application in Curcumin Delivery for Dermal Wound Healing in Rat. BioMed Research International, 2009, Article ID: 595126. https://doi.org/10.1155/2009/595126
[28]
Vinklárková, L., et al. (2017)Film Wound Dressing with Local Anesthetic Based on Insoluble Carboxymethycellulose Matrix. Journal of Applied Biomedicine, 15, 313-320. https://doi.org/10.1016/j.jab.2017.08.002
[29]
Islam, M.S., et al. (2017)Core-Shell Drug Carrier from Folate Conjugated Chitosan Obtained from Prawn Shell for Targeted Doxorubicin Delivery. Journal of Materials Science: Materials in Medicine, 28, Article No. 55. https://doi.org/10.1007/s10856-017-5859-x
[30]
Balakrishnan, B., et al. (2005)Evaluation of an in Situ Forming Hydrogel Wound Dressing Based on Oxidized Alginate and Gelatin. Biomaterials, 26, 6335-6342. https://doi.org/10.1016/j.biomaterials.2005.04.012
[31]
Bhowmik, S., et al. (2017)Reinforcement of Gelatin-Based Nanofilled Polymer Biocomposite by Crystalline Cellulose from Cotton for Advanced Wound Dressing Applications. Polymers, 9, Article 222. https://doi.org/10.3390/polym9060222
[32]
Parvez, S., et al. (2012)Preparation and Characterization of Artificial Skin Using Chitosan and Gelatin Composites for Potential Biomedical Application. Polymer Bulletin, 69, 715-731. https://doi.org/10.1007/s00289-012-0761-7
[33]
Patra, P., et al. (2014)Ciprofloxacin Conjugated Zinc Oxide Nanoparticle: A Camouflage towards Multidrug Resistant Bacteria. Bulletin of Materials Science, 37, 199-206. https://doi.org/10.1007/s12034-014-0637-6
[34]
Sharma, D., et al. (2010)Synthesis of ZnO Nanoparticles and Study of Their Antibacterial and Antifungal Properties. Thin Solid Films, 519, 1224-1229. https://doi.org/10.1016/j.tsf.2010.08.073
[35]
Mino, G. and Kaizerman, S. (1958) A New Method for the Preparation of Graft Copolymers. Polymerization Initiated by Ceric Ion Redox Systems. Journal of Polymer Science, 31, 242-243. https://doi.org/10.1002/pol.1958.1203112248
[36]
Singh, D.K. and Ray, A.R. (1998) Characterization of Grafted Chitosan Films. Carbohydrate Polymers, 36, 251-255. https://doi.org/10.1016/S0144-8617(97)00260-9
[37]
Rahman, P.M., Abdul Mujeeb, V.M., Muraleedharan, K. and Thomas, S.K.(2018)Chitosan/Nano ZnO Composite Films: Enhanced Mechanical, Antimicrobial and Dielectric Properties. Arabian Journal of Chemistry, 11, 120-127. https://doi.org/10.1016/j.arabjc.2016.09.008
[38]
Mahmud, M., Daik, R. and Adam, Z. (2018) Influence of Poly (Ethylene Glycol) on the Characteristics of γ Radiation-Crosslinked Poly (Vinyl Pyrrolidone)-Low Molecular Weight Chitosan Network Hydrogels. Sains Malaysiana, 47, 1189-1197. https://doi.org/10.17576/jsm-2018-4706-14
[39]
Felinto, M.C., et al. (2007)The Swelling Behavior of Chitosan Hydrogels Membranes Obtained by UV-and γ-Radiation. Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, 265, 418-424. https://doi.org/10.1016/j.nimb.2007.09.025
[40]
Johnson, Z.I., et al. (2019)The Role of Chemokines in Fibrotic Dermal Remodeling and Wound Healing. In: Willis, M.S., Yates, C.C. and Schisler, J.C., Eds., Fibrosis in Disease, Humana, Cham, 3-24. https://doi.org/10.1007/978-3-319-98143-7_1