Preparation of Nanocomposite Systems Based on Natural Polymers and Clay for Controlled Release of Cisplatin

Document Type : Research Article


1 Department of Chemistry, Faculty of Sciences, Azarbaijan Shahid Madani University

2 Department of Applied Chemistry, Faculty of Chemistry, University of Tabriz, Tabriz, Iran


In this study, after the preparation of unsaturated polyester with various ratios of anhydride monomers, the effects of nano silicate on the polymerization, curing behavior, and mechanical properties were investigated. The unsaturated polyester resin was synthesized at various molar ratios of anhydride monomers (maleic/phthalic: 10 to 90%) and propylene glycol. Acid number measurement was used to evaluate polymerization. With an increase in the molar maleic content, the time of polymerization reaction and the acidic number increased. In the next step, the resin was cured with an accelerator and initiator, and styrene monomer. curing behavior was determined using a curing curve and gelation time measurement. The curing curve showed that by increasing the maleic anhydride monomer ratio from 10% to 90%, the curing time decreased by 77%, and the maximum thermogenic temperature increased by 24%. Increasing the maleic content from 10 to 90% resulted in tensile strength changes from 11 to 70 MPa and tensile modulus from 60 to 359 MPa. The impact strength and the heat distortion temperature increased and became plateaued at higher maleic percentages. The nanocomposites were prepared with 50 mol% maleic anhydrides, containing 2, 4, 6, and 8 wt.% of nano silicate. By increasing the amount of nanoclay, the curing time decreased and the maximum exothermic temperature increased. Mechanical properties were evaluated by using Heat Deflection Temperature (HDT), tensile properties, impact strength, and surface hardness tests. The impact strength and the heat distortion temperature also showed an upward trend with an increase in the amount of nano, even in small quantities. By adding 8% nanoclay to the matrix, the impact strength and heat deflection temperature increased by 11% and 13%.


[1] Greco F., Vicent M.J., Combination Therapy: Opportunities and Challenges for Polymer-Drug Conjugates as Anticancer Nanomedicines, Advanced Drug Delivery Reviews, 61(13): 1203-1213 (2009).
[2] Deb A., Andrews N.G., Raghavan V., Natural Polymer Functionalized Graphene Oxide for Co-delivery of Anticancer Drugs: In-Vitro and in-Vivo, International Journal of Biological Macromolecules, 113: 515-525 (2018).
[3] نبی تیر، م.، آقامیری، س.ف.، طلائی خوزانی، م.ر.، بررسی آزمایشگاهی تأثیر پوشش دهی کیتوسان در کاهش تجمع نانولوله­ های کربنی به عنوان حامل داروی ضد سرطان کوئرستین، نشریه شیمی و مهندسی شیمی ایران، (3)36: 93 تا 102 (1396)
[5] Reis A.V., Guilherme M.R. Moia T.A., Mattoso L.H.C., Muniz E.C., Tambourgi E.B., Synthesis and Characterization of a Starch‐Modified Hydrogel as Potential Carrier for Drug Delivery System, Journal of Polymer Science Part A: Polymer Chemistry, 46: 2567-2574 (2008).
[7] Maghsoodi V., Yaghmaei S., Beigi S.M., Influence of Different Nitrogen Sources on Amount of Chitosan Production by Aspergillusniger in Solid State Fermentation, Iranian Journal of Chemistry and Chemical Engineering (IJCCE), 27(1): 47-52 (2008).
[8] Li P., Wang Y., Peng Z., She F., Kong L., Development of Chitosan Nanoparticles as Drug Delivery Systems for 5-Fuorouracil and Leucovorin Blends, Carbohydrate Polymers, 85: 698-704 (2011).
[9] Farshi Azhar F., Shahbazpour E., Olad A., pH Sensitive and Controlled Release System Based on Cellulose Nanofibers-poly Vinyl Alcohol Hydrogels for Cisplatin Delivery, Fibers and Polymers, 18(3): 416-423 (2017).
[10] Gonzalez V.M., Fuertes M.A., Alonso C., Perez J.M., Is Cisplatin-Induced Cell Death Always Produced by Apoptosis, Molecular Pharmacology, 59: 657-663 (2001).
[11] Kelland L., The Resurgence of Platinum-Based Chemotherapy, Nature Reviews, 7: 573-584 (2007).
[13] Feng S.S., Mei L., Anitha P., Gan C.W., Zhou W., Poly (lactide)–Vitamin E Derivative/Montmorillonite Nanoparticle Formulations for the Oral Delivery of Docetaxel, Biomaterials, 30: 3297-3306 (2009).
[14] Yu C.Y., Zhang X.C., Zhou F.Z., Zhang X.Z., Cheng S.X., Zhuo R.X., Sustained Release of Antineoplastic Drugs from Chitosan-Reinforced Alginate Microparticle Drug Delivery Systems, International Journal of Pharmaceutics, 357(1-2): 15-21 (2008).
[15] Viseras C., Cerezo P., Sanchez, R., Salcedo I., Aguzzi C., Current Challenges in Clay Minerals for Drug Delivery, Applied Clay Science, 48(3): 291-295 (2010).
[16] Yang J.H., Lee J.H., Ryu H.J., Elzatahry A.A., Alothman Z.A., Choy J.H., Drug–Clay Nanohybrids as Sustained Delivery Systems, Applied Clay Science, 130: 20-32 (2016)
[18] Iliescu R.I., Andronescu E., Voicu G., Ficai A., Covaliu C.I., Hybrid Materials Based on Montmorillonite and Citostatic Drugs: Preparation and Characterization, Applied Clay Science, 52: 62-68 (2011).
[19] Carretero M.I., Pozo M., Clay and Non-Clay Minerals in the Pharmaceutical Industry: Part I. Excipients and Medical Applications, Applied Clay Science, 46: 73-80 (2009).
[20] Joshi G.V., Kevadiya B.D., Patel H.A., Bajaj H.C., Jasra R.V., Montmorillonite as a Drug Delivery System: Intercalation and in Vitro Release of Timolol Maleate, International Journal of Pharmaceutics, 374: 53-57 (2009).
[21] Joshi G.V., Patel H.A., Kevadiya B.D., Bajaj H.C., Montmorillonite Intercalated with Vitamin B1 as Drug Carrier, Applied Clay Science, 45: 248-253 (2009).
[22] Baek M., Lee J.A., Choi S.J., Toxicological Effects of a Cationic Clay, Montmorillonite in Vitro and in Vivo, Molecular & Cellular Toxicology, 8: 95-101 (2012).
[23] Salcedo I., Aguzzi C., Sandri G., Bonferoni M.C., Mori M., Cerezo P., Sanchez R., Viseras C., Caramella C., In Vitro Biocompatibility and Mucoadhesion of Montmorillonite Chitosan Nanocomposite: A New Drug Delivery, Applied Clay Science, 55: 131-137 (2012).
[24] Liu Q., Liu, Y., Xiang S., Mo X., Su S., Zhang J., Apoptosis and Cytotoxicity of Oligo (Styrene-co-Acrylonitrile)-Modified Montmorillonite, Applied Clay Science, 51: 214-219 (2011).
[25] Lee Y.H., Kuo T.F., Chen B.Y., Feng Y.K., Wen Y.R., Lin W.C., Lin F.H., Toxicity Assessment of Montmorillonite as a Drug Carrier for Pharmaceutical Applications: Yeast and Rats Model, Biomedical Engineering Applications Basis and Communications, 17: 12-18 (2005)
[28] قنبرزاده، ب.، ابوالقاسمی فخری، ل.، دهقان نیا، ج.، انتظامی، ع.ا.، مقایسه نفوذ پذیری، زاویه تماس و ویژگی های گرمایی نانو چندسازه های بر پایه کربوکسی متیل سلولز دارای دو نوع نانو پرکننده: نانو رس و نانو ویسکر سلولز، نشریه شیمی و مهندسی شیمی ایران، (3)32: 13 تا 24 (1392)
[29] Oun R., Plumb J.A., Wheate N.J., A Cisplatin Slow-Release Hydrogel Drug Delivery System Based on a Formulation of the Macrocycle Cucurbituril, Gelatin and Polyvinyl Alcohol, Journal of inorganic biochemistry, 134: 100-105 (2014).
[30] Moura M., Gil M., Figueiredo M., Delivery of Cisplatin from Thermosensitive Co-Cross-Linked Chitosan Hydrogels, European Polymer Journal, 49: 2504-2510 (2013).
[31] Yan X., Gemeinhart R.A., Cisplatin Delivery from Poly (Acrylic Acid-co-Methyl Methacrylate) Microparticles, Journal of Controlled Release, 106: 198-208 (2005).
[32] Cheng C., Xia D., Zhang, X., Biocompatible Poly(N-Isopropylacrylamide)-g-Carboxymethyl Chitosan Hydrogels as Carriers for Sustained Release of Cisplatin, Journal of Materials Science, 50: 4914-4925 (2015).
[33] Peng J., Qi T., Liao J, Controlled Release of Cisplatin from pH-Thermal Dual Responsive Nanogels, Biomaterials, 34: 8726-8740 (2013).
[34] Likhitkar S., Bajpai A.K., Magnetically Controlled Release of Cisplatin from Superparamagnetic Starch Nanoparticles, Carbohydrate Polymers, 87: 300-308 (2012).
[35] Cho S., Sun Y., Jarboe E.A., Soisson A.P., Dodson M.K., Gaffney D.K., Peterson C.M., Janát-Amsbury M.M., Mucoadhesive Hybrid Gel Improves Intraperitoneal Platinum Delivery, International Journal of Pharmaceutics, 458: 148-155 (2013).
[36] Rajan M., Murugan M., Ponnamma D., Sadasivuni K.K., Munusamy M.A., Poly-Carboxylic Acids Functionalized Chitosan Nanocarriers for Controlled and Targeted anti-Cancer Drug Delivery, Biomedicine & Pharmacotherapy, 83: 201-211 (2016).
[37] Papadimitriou S., Bikiaris D., Avgoustakis K., Karavas, E., Georgarakis, M., Chitosan Nanoparticles Loaded with Dorzolamide and Pramipexole, Carbohydrate Polymers, 73: 44-54 (2008).
[38] Xing, J., Deng, L., Dong, A., Chitosan/Alginate Nanoparticles Stabilized by Poloxamer for the Controlled Release of 5-Fluorouracil, Journal of Applied Polymer Science, 117: 2354-2359 (2010).
[39] Higuchi T., Mechanism of Sustained Medication. Theoretical Analysis of Rate of Release of Solid Drugs Dispersed in Solid Matrices, Journal of Pharmaceutical Science, 52(12): 1145-1149 (1963).
[40] Korsmeyer, R.W., Gurny, R., Doelker, E., Buri, P., Peppas, N.A., Mechanisms of Solute Release from Porous Hydrophilic Polymers, International Journal of Pharmaceutics, 15(1): 25-35 (1983).
[41] Pasparakis, G., Bouropoulos, N., Swelling Studies and in vitro Release of Verapamil from Calcium Alginate and Calcium Alginate-Chitosan Beads, International Journal of Pharmaceutics, 323: 34-42 (2006).
[42] Pendekal M.S., Tegginamat P.K., Hybrid Drug Delivery System for Oropharyngeal, Cervical and Colorectal Cancer- in Vitro and in Vivo Evaluation, Saudi Pharmaceutical Journal, 21(2): 177-186 (2013).
[43] Jung S.-W., Jeong Y.-I., Kim Y.-H., Choi K.-C., Kim S.-H., Drug Release from Core-Shell Type Nanoparticles of Poly (DL-lactide-co-glycolide)-grafted Dextran, Journal of Microencapsulation, 22: 901-911 (2005).
[45] Joshi G.V., Kevadiya B.D., Patel H.A., Bajaj H.C., Jasra R.V., Montmorillonite as a Drug Delivery System: Intercalation and in Vitro Release of Timolol Maleate, International Journal of Pharmaceutics, 374: 53-57 (2009).
[46] Wang L., Wang A., Adsorption Characteristics of Congo Red onto the Chitosan/Montmorillonite Nanocomposite, Journal of Hazardous Materials, 147: 979-985 (2007).
[47] Celis R., Adelino M., Hermosín M., Cornejo J., Montmorillonite-Chitosan Bionanocomposites as Adsorbents of the Herbicide Clopyralid in Aqueous Solution and Soil/Water Suspensions, Journal of Hazardous Materials, 209: 67-76 (2012).
[48] Namazi H., Dadkhah A., Mosadegh M., New Biopolymer Nanocomposite of Starch-Graft Polystyrene/Montmorillonite Clay Prepared Through Emulsion Polymerization Method, Journal of Polymers and the Environment, 20: 794-800 (2012).
[49] Vijaya Y., Popuri S.R., Boddu V.M., Krishnaiah A., Modified Chitosan and Calcium Alginate Biopolymer Sorbents for Removal of Nickel (II) Through Adsorption, Carbohydrate Polymers, 72: 261-271 (2008).
[50] Tseng C.L., Yang K.C., Yen K.C., Wu S.Y.H., Lin F.H., Preparation and Characterization of Cisplatin-Incorporated Gelatin Nanocomplex for Cancer Treatment, Current Nanoscience, 7: 932-937 (2011).
[51] Namazi H., Dadkhah A., Mosadegh M., New Biopolymer Nanocomposite of Starch-Graft Polystyrene/Montmorillonite Clay Prepared through Emulsion Polymerization Method, Journal of Polymer and Environment, 20: 794-800 (2012).
[52] Huang M., Yu J., Structure and Properties of Thermoplastic Corn Starch/Montmorillonite Biodegradable Composites, Journal of Applied Polymer Science, 99: 170-176 (2006).
[53] Saikia J.P., Banerjee S., Konwar B.K., Kumar A., Biocompatible Novel Starch/Polyaniline Composites: Characterization, Anti-Cytotoxicity and Antioxidant Activity, Colloids and Surfaces B: Biointerfaces, 81: 158-164 (2010).
[54] Olad A., Farshi Azhar F., A Study on the Adsorption of Chromium (VI) from Aqueous Solutions on the Alginate-Montmorillonite/Polyaniline Nanocomposite, Desalination and Water Treatment, 52: 13-15 (2014).
[55] Li Y., Zhao X., Xu Q., Zhang Q., Chen D., Facile Preparation and Enhanced Capacitance of the Polyaniline/Sodium Alginate Nanofiber Network for Supercapacitors, Langmuir, 27: 6458-6463 (2011).
[56] Raj V., Prabha G., Synthesis, Characterization and in Vitro Drug Release of Cisplatin Loaded Cassava Starch Acetate–PEG/Gelatin Nanocomposites, Journal of the Association of Arab Universities for Basic and Applied Sciences, 21: 10-16 (2016).
[57] Cypes S.H., Saltzman W.M., Giannelis E.P., Organosilicate-Polymer Drug Delivery Systems: Controlled Release and Enhanced Mechanical Properties, Journal of Controlled Release, 90: 163-169 (2003).