In vivo Acute Cytotoxicity Study of Poly(2-amino ethyl methacrylate-co-methylene bis-acrylamide) Magnetic Composite Synthesized in Supercritical CO2

Gunjan Bisht; M. G. H. Zaidi; Biplab KC

Macromolecular Research, Vol.26, No.7, 581-591, July, 2018

DOI10.1007/s13233-018-6080-6 Export Citation

In vivo Acute Cytotoxicity Study of Poly(2-amino ethyl methacrylate-co-methylene bis-acrylamide) Magnetic Composite Synthesized in Supercritical CO2

Gunjan Bisht^†, M. G. H. Zaidi¹, and Biplab KC²

Department of Chemical Science and Engineering, School of Engineering, Kathmandu University, Nepal
¹Department of Chemistry, College of Basic Science, G.B. Pant University of Agriculture and Technology, Pantnagar, India
²Department of Biotechnology, School of Science, Kathmandu University, Nepal

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With magnetic ferrite nanoparticles (FNPs) gaining interest in biotechnological fields and methacrylates being used as synthetic polymer for therapeutics loading and conjugation, we attempt to make novel magnetic composite by supercritical CO2 assisted entrapment of FNPs into in situ synthesized polymeric mesh of 2-amino ethyl methacrylate (AEMA) cross linked with methylene bis-acrylamide (MBA) at90±1 oC and pressure of 1200 psivia 2,2-azobisisobutyronitrile (AIBN) initiated radical polymerization. Particle thus obtained was characterized by using proton nuclear magnetic resonance (1H NMR), X-ray diffraction (XRD), thermal gravimetric-derivative thermogravimetric-differential thermal analysis (TG-DTGDTA), atomic force microscopy (AFM), and vibrating sample magnetometer (VSM). 1H NMR of Copolymer (without FNPs embedded) demonstrated distinct peaks verifying AEMA moieties flanked by MBA moieties with free amino group. Though the particle showed less saturation magnetization than that of as synthesized FNPs, it still maintained similar magnetic profile. AFM results showed average grain size of polymeric magnetic composites (PMCs) to be 80 nm with less agglomeration. TGA results verify the thermal stability of the compound upto 200 oC. In vivo acute cytotoxicity was profiled by administrating four different concentrations of FNPs, Copolymer and PMCs (FNPs embedded) into Sprague Dawley albino rat intraperitonally for 14 days and measuring various hematological, biochemical and serum enzymatic parameters along with histological examinations. Overall, PMCs showed no significance change in these parameters compared to normal saline administered control which signifies biocompatible nature of the composite. Hence, clean synthesis of FNPs embedded biocompatible amino functional magnetic composite has been achieved which holds potential in number of applications like drug loading, enzyme immobilizations, targeted therapy, etc.

Keywords:poly(AEMA-co-MBA);magnetic composites;supercritical CO2;in situ polymerization;in vivo cytotoxicity

[References]

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[2] Salata OV, J. Nanobiotechnol., 2, 3 (2004)

[3] Bloemen M, Brullot W, Luong TT, Geukens N, Gils A, Verbiest T, J. Nanopart. Res., 14, 1100 (2012)

[4] Kc B, Paudel SN, Rayamajhi S, Karna D, Adhikari S, Shrestha BG, Bisht G, Chem. Cent. J., 10, 16 (2016)

[5] Piotrowska A, Leszczuk E, Bruchertseifer F, Morgenstern A, Bilewicz A, J. Nanopart. Res., 15, 2082 (2013)

[6] Sette A, Spadavecchia J, Landoulsi J, Casale S, Haye B, Crociani O, Arcangeli A, J. Nanopart. Res., 15, 2111 (2013)

[7] Szpak A, Fiejdasz S, Prendota W, Straczek T, Kapusta C, Szmyd J, Nowakowska M, Zapotoczny S, J. Nanopart. Res., 16, 2678 (2014)

[8] Pimpha N, Sunintaboon P, Inphonlek S, Tabata Y, J. Biomater. Sci.-Polym. Ed., 21, 205 (2010)

[9] Ji WH, Panus D, Palumbo RN, Tang RP, Wang C, Biomacromolecules, 12(12), 4373 (2011)

[10] Kang XJ, Dai YL, Ma PA, Yang DM, Li CX, Hou ZY, Cheng ZY, Lin J, Chemistry, 18, 15676 (2012)

[11] Tiwari DK, Behari J, Sen P, World Appl. Sci. J., 3, 417 (2008)

[12] Ahmad R, Sardar M, Biochem. Anal. Biochem., 4, 178 (2015)

[13] Misson M, Zhang H, Jin B, J. R. Soc. Interface, 12 (2015)

[14] Davis ME, Chen ZG, Shin DM, Nat. Rev. Drug Discov., 7, 771 (2008)

[15] Ma P, Mumper RJ, Nano Today, 8(3), 313 (2013)

[16] Crucho CI, Chem. Med. Chem., 10, 24 (2015)

[17] Jun YW, Jang JT, Cheon J, Adv. Exp. Med. Biol., 620, 85 (2007)

[18] Akbarzadeh A, Zarghami N, Mikaeili H, Asgari D, Goganian AM, Khiabani HK, Samiei M, Davaran S, Nanotechnol. Sci. Appl., 5, 13 (2012)

[19] Wu W, He Q, Jiang C, Nanoscale Res. Lett., 3, 397 (2008)

[20] Bisht G, Rayamajhi S, Kc B, Paudel SN, Karna D, Shrestha BG, Nanoscale Res. Lett., 11, 537 (2016)

[21] Cheng Q, Huang Y, Zheng H, Wei T, Zheng S, Huo S, Wang X, Du Q, Zhang X, Zhang HY, Liang XJ, Wang C, Tang R, Liang Z, Biomaterials, 34, 3120 (2013)

[22] Jiang XZ, Liu SY, Narain R, Langmuir, 25(23), 13344 (2009)

[23] You YZ, Manickam DS, Zhou QH, Oupicky D, J. Control. Release, 122, 217 (2007)

[24] Hong K, Zhang H, Mays JW, Visser AE, Brazel CS, Holbrey JD, Reichert WM, Rogers RD, Chem. Commun., 1368 (2002).

[25] Zaidi MGH, Bhullar N, Sharma D, Agarwal V, Alam S, Rai AK, Pant RP, J. Nanostruct. Polym. Nanocompos, 6, 103 (2007)

[26] Bisht G, Zaidi MG, Drug Deliv. Transl. Res., 5, 268 (2015)

[27] Vennerberg D, Hall R, Kessler MR, Polymer, 55(16), 4156 (2014)

[28] Kankala RK, Zhang YS, Wang SB, Lee CH, Chen AZ, Adv. Healthc. Mater., 6 (2017)

[29] Kazarian SG, Polym. Sci. Ser. C, 42, 78 (2000)

[30] Bisht G, Neupane S, Makaju R, J. Nanomater., 2192647 (2016).

[31] Chen BQ, Kankala RK, Chen AZ, Yang DZ, Cheng XX, Jiang NN, Zhu K, Wang SB, Int. J. Nanomedicine, 12, 1877 (2017)

[32] Jain NC, Schalm’s Veterinary Haematology, Lea and Febiger, Philadelphia, 1986.

[33] Chauhan RS, Agarwal DK, Text book of Veterinary Clinical & Laboratory Diagnosis, Jaypee Brothers Medical Publishers, Ltd., New Delhi, 2006.

[34] Natt MP, Herrick CA, Poult. Sci., 31, 735 (1952)

[35] Koller A, in Clinical Chemistry: Theory, Analysis and Correlation, Kaplan LA, Pesce AJ, Eds., Mosby, Toronto, 1984, pp 1268-1327.

[36] Gendler S, in Clinical Chemistry: Theory, Analysis and Correlation, 2nd ed., Kaplan LA, Pesce AJ, Eds., Mosby, pp 1029-1065 1989.

[37] Warnick GR, Knopp RH, Fitzpatrick V, Branson L, Clin. Chem., 36, 15 (1990)

[38] Murray RL, in Clinical Chemistry: Theory, Analysis and Correlation, Kaplan LA, Pesce AJ, Eds., Mosby, Toronto, pp 1247-1253 1984.

[39] Moss DW, Henderson AK, in Textbook of Clinical Chemistry, Burtis CA, Ashwood ER, Eds., Saunders, Co., Philadelphia, pp 617-721 1994.

[40] Snedecor GW, Cochran WG, Statistical Methods, 8th ed., Iowa State University Press, Iowa, Ames, 1989.

[41] Odian G, in Principles of Polymerization, John Wiley & Sons, Hoboken, p 230 2004.

[42] Blaney L, Lehigh Rev., 15 (2007)

[43] Lopez JA, Gonzalez F, Bonilla FA, Zambrano G, Gomez ME, Rev. LatinAm. Metal. Mat., 30, 60 (2010)

[44] Haugstad G, in Overview of AFM. Atomic Force Microscopy: Understanding Basic Modes and Advanced Applications, John Wiley & Sons, Inc., Hoboken, pp 1-32 2012.

[45] Raposo M, Ferreira Q, Ribeiro PA, in Modern Research and Educational Topics in Microscopy, Formatex, Badajoz, pp 758-769 2007.

[46] Aas CJ, Hanip PJ, Cuadrado R, Plotnikova EM, Szunyogh L, Udvardi L, Chantrell RW, Phys. Rev. B, 88, 174409 (2013)

[47] Busher J, Clinical Methods: The History, Physical, and Laboratory Examinations, Butterworth Publishers, Boston, Butterworths, 1990.