Synthesis and characterization of poly(N-isopropylmethacrylamide-co-N-isopropylacrylamide) copolymers

Maja Z. Urošević, Ljubiša B. Nikolić, Snežana Ilić-Stojanović, Aleksandar Zdravković, Vesna Nikolić

Abstract


Copolymeric hydrogels of poly(N-isopropylmethacrylamide-co-N-isopropylacrylamide), p(NIPMAM/NIPAM), are synthesized by radical polymerization of N-isopropylmethacryl­amide (NIPMAM) and N-isopropylacrylamide (NIPAM) monomers by using the cross-linker ethylen glycol dimethacrylate (EGDM). The synthesized copolymeric p(NIPMAM/NIPAM) hydrogels, starting monomers and the cross-linker were structurally characterized by using Fourier transform infrared spectroscopy (FTIR). The amounts of residual reactants in the synthesized hydrogels were determined by high-pressure liquid chromatography (HPLC). Swelling of p(NIPMAM/NIPAM) hydrogels was investigated in relation to the temperature and pH value of the solution. The obtained values of residual monomer quantities are within acceptable limits and in the range from 2.69 to 5.25 mg g-1 for NIPMAM and 14.55 to 30.80 mg g-1 for NIPAM. The synthesized p(NIPMAM/NIPAM) hydrogels are negatively thermosensitive. The most common mechanisms of transport of a swelling solution in p(NIPMAM/NIPAM) hydrogels are polymer chain relaxation, (Case III), and the anomalous type of diffusion (non-Fickian diffusion). The maximal equilibrium swelling degree of 51.19 was reached by the p(NIPMAM/NIPAM) hydrogel with 1.5 mol% of EGDM at the temperature of 25 oC and pH 4, whereas the lowest one of 0.98 was exhibited by the hydrogel with 3 mol% of EGDM at the temperature of 80 oC and pH 7. Due to their low content of residual reactants and a satisfactory degree of swelling at various pH values, synthesized p(NIPMAM/NIPAM) hydrogels can be applied as carriers for the controlled release of pharmaceutically active substances.


Keywords


hydrogel; swelling; FTIR; HPLC

Full Text:

PDF (1,092 kB)

References


Shetye SP, Godbole A, Bhilegaokar S, Gajare P. Hydrogels: Introduction, Preparation, Characterization and Applications. IJRM Human. 2015; 1: 47-71.

Ashraf S, Park HK, Park H, Lee SH. Snapshot of phase transition in thermoresponsive hydrogel PNIPAM: Role in drug delivery and tissue engineering. Macromol Res. 2016; 24: 297-304.

Varaprasad K, Raghavendra GM, Jayaramudu T, Yallapu MM, Sadiku R. A mini review on hydrogels classification and recent developments in miscellaneous applications. Mater Sci Eng C. 2017; 79: 958-971.

Das N. Preparation methods and properties of hydrogel: a review. Int J Pharm Sci. 2013; 5: 112-117.

Chai Q, Jiao Y, Yu X. Hydrogels for biomedical applications: their characteristics and the mechanisms behind them. Gels 2017; 3: 1-15.

Liu Z, Faraj Y, Ju XJ, Wang W, Xie R, Chu LY. Nanocomposite smart hydrogels with improved responsiveness and mechanical properties: A mini review. J Polym Sci Pol Phys. 2018; 56: 1306-1313.

Shidhaye S, Badshah F, Prabhu N, Parikh P. Smart Polymers: A Smart Approach to Drug Delivery. World J Pharm Res. 2014; 3: 159-172.

Mahajan A, Aggarwal G. Smart polymers: innovations in novel drug delivery. Int J Drug Dev Res. 2011; 3: 16-30.

Almeida H, Amaral MH, Lobão P. Temperature and pH stimuli-responsive polymers and their applications in controlled and selfregulated drug delivery. J Appl Pharm Sci. 2012; 2:1-10.

Hilmi B, Abdul Hamid ZA, Akil HM, Yahaya BH. The Characteristics of the Smart Polymers Temperature or pH-responsive hydrogel. Procedia Chem. 2016; 19: 406-409.

Samal SK, Dash M, Dubruel P, Van Vlierberghe S. Smart polymer hydrogels: properties, synthesis and applications. In: Aguilar MR, Román JS, eds. Smart polymers and their applications. Cambridge, UK: Woodhead; 2014: 237-270.

Omidian H, Park K. Introduction to hydrogels. In: Ottenbrite RM, Park K, Okano T, eds. Biomedical applications of hydrogels handbook. New York, NY: Springer; 2010: 1-16.

Peppas NA, Bures P, Leobandung W, Ichikawa H. Hydrogels in pharmaceutical formulations. Eur J Pharm Biopharm. 2000; 50: 27–46.

Ganji F, Vasheghani-Farahani S, Vasheghani-Farahani E. Theoretical Description of Hydrogel Swelling: A Review. Iran Polym J. 2010; 19: 375-398.

Gemeinhart RA, Guo C. Fast Swelling Hydrogel Systems. In: Yui N, Mrsny RJ, Park K, eds. Reflexive polymers and hydrogels: understanding and designing fast responsive polymeric systems. Boca Raton: CRC Press; 2004: 245-257.

Firestone BA, Siegel RA. Kinetics and mechanisms of water sorption in hydrophobic, ionizable copolymer gels. J Appl Polym Sci. 1991; 43: 901-914.

Peppas NA, Barr-Howell BD. Characterization of the Crosslinked Structure of Hydrogels. In: Peppas NA, ed. Hydrogelsin Medicine and Pharmacy. Vol. 1. Boca Raton, FL: CRC Press. 1986: 27-56.

Peppas NA Khare AR. Preparation, structure and diffusional behavior of hydrogels in controlled release. Adv Drug Deliv Rev. 1993; 11: 1-35.

Wang J, Wu W, Lin Z. Kinetics and thermodynamics of the water sorption of 2‐hydroxyethyl methacrylate/styrene copolymer hydrogels. J Appl Polym Sci. 2008; 109: 3018-3023.

Bajpai SK. Swelling–deswelling behavior of poly(acrylamide‐co‐maleic acid) hydrogels. J Appl Polym Sci. 2001; 80: 2782-2789.

Ritger PL, Peppas NA. A simple equation for description of solute release II. Fickian and anomalous release from swellable devices. J Control Release. 1987; 5: 37-42.

Torres-Lugo M, Peppas NA. Molecular Design and in Vitro Studies of Novel pH-Sensitive Hydrogels for the Oral Delivery of Calcitonin. Macromolecules. 1999; 32: 6646-6651.

Crank J. The Mathematics of Diffusion. Oxford: Clarendon Press; 1975

Hansen CM. The significance of the surface condition in solutions to the diffusion equation: explaining “anomalous” sigmoidal, Case II, and Super Case II absorption behavior. Eur Polym J. 2010; 46: 651-662.

Khare AR, Peppas NA. Swelling/deswelling of anionic copolymer gels. Biomaterials. 1995; 16: 559-567.

Mercea P. Models for Diffusion in Polymers. In: Piringer OG, Baner AL, eds. Plastic Packaging: Interactions with Food and Pharmaceuticals. Weinheim:Wiley-VCH; 2008: 123-162.

Cai S, Suo Z. Mechanics and chemical thermodynamics of phase transition in temperature-sensitive hydrogels. J Mech Phys Solids. 2011; 59: 2259-2278.

Ebara M, Kotsuchibashi Y, Narain R, Idota N, Kim YJ, Hoffman JM, Uto K, Aoyagi T. Smart Biomaterials. Tokyo: Springer Japan; 2014.

Grassi G, Farra R, Caliceti P, Guarnieri G, Salmaso S, Carenza M, Grassi M. Temperature-sensitive hydrogels. Potential Therapeutic Applications. Am J Drug Deliv. 2005; 3: 239-251.

Augé A, Zhao Y. What determines the volume transition temperature of UCST acrylamide–acrylonitrile hydrogels? RSC Adv. 2016; 6: 70616-70623.

Ding Z, Wang C, Feng G, Zhang X. Thermo-responsive fluorescent polymers with diverse LCSTs for ratiometric temperature sensing through FRET. Polym. 2018; 10: 283.

Heskins M, Guillet JE. Solution properties of poly (N-isopropylacrylamide). J Macromol Sci A. 1968; 2: 1441-1455.

Djokpe E, Vogt W. N-Isopropylacrylamide and N-Isopropylmethacrylamide: Cloud Points of Mixtures and Copolymers. Macromol Chem Phys. 2001; 202: 750-757.

Gutowska A, Bae YH, Feijen J, Kim SW. Heparin release from thermosensitive hydrogels. J Control Release. 1992; 22:95-104.

Fundueanu G, Constantin M, Bucatariu S, Ascenzi P. Poly (N‐isopropylacrylamide‐co‐N‐isopropylmethacrylamide) Thermo‐Responsive Microgels as Self‐Regulated Drug Delivery System. Macromol Chem Phys. 2016; 217:2525-2533.

Jung SC, Bae YC. The effects of interaction energy on the volume phase transition of N-isopropylacrylamide-co-N-isopropylmethacrylamidenano-sized gel particles: Applicability of molecular simulation technique. Polym. 2009; 50: 4957-4963.

Starovoytova L, Spěvaček J, Ilavský M. 1H NMR study of temperature-induced phase transitions in D2O solutions of poly(N-isopropylmethacrylamide)/poly(N-isopropylacrylamide) mixtures and random copolymers. Polym. 2005; 46: 677-683.

Kokufuta MK, Sato S, Kokufuta E. LCST behavior of copolymers of N-isopropylacrylamide and N-isopropylmethacrylamide in water. Colloid Polym Sci. 2012; 290:1671-1681.

Berndt I, Richtering W. Doubly Temperature Sensitive Core-Shell Microgels, Macromolecules. 2003; 36: 8780-8785.

Naseem K, Farooqi ZH, Begum R, Ghufran M, Rehman MZU, Najeeb J, Irfan A, Al-Sehemi AG. Poly (N-isopropylmethacrylamide-acrylic acid) microgels as adsorbent for removal of toxic dyes from aqueous medium. J Mol Liq. 2018; 268: 229-238.

Rwei SP, Tuan HNA, Chiang WY, Way TF. Synthesis and characterization of pH andthermo dual-responsive hydrogels with a semi-IPN structure based on N-Isopropylacrylamide and Itaconamic Acid. Materials. 2018; 11: 696.

Zdravković AS, Nikolić LB, Ilić-Stojanović SS, Nikolić VD, Savić SR, Kapor AJ. The evaluation of temperature and pH influences on equilibrium swelling of poly(N-isopropylacrylamide-co-acrylic acid) hydrogels. Hem Ind. 2017; 71:395-405.

Rwei SP, Anh THN, Chiang WY, Way TF, Hsu YJ. Synthesis and drug delivery application of thermo-and pH-sensitive hydrogels: poly(β-CD-co-N-isopropylacrylamide-co-IAM). Materials. 2016; 9: 1003.

Kurečič M, Sfiligoj-Smole M, Stana-Kleinschek K. UV polymerization of poly(N-isopropylacrylamide) hydrogel. Mater Technol. 2012; 46:87-91.

Shah LA, Farooqi ZH, Naeem H, Shah SM, Siddiq M. Synthesis and characterization of poly(N-isopropylacrylamide) hybrid microgels with different cross-linker contents. J Chem Soc Pak. 2013; 35: 1522-1529.

Tang XL, Guo SM, Liu ZD, Tang RZ, Pang JY, Chen Y. Preparation of thermo-sensitive poly(N-isopropylacrylamide) film using KHz alternating current Dielectric barrier discharge. In: Proceedings of the 2017 3rd International Forum on Energy, Environment Science and Materials (IFEESM 2017). Shenzhen, China, 2017, pp. 598-602.

Ayman AD. The residual monomer content and mechanical properties of CADCAM resins used in the fabrication of complete dentures as compared to heat cured resins. Electron Physician. 2017; 9: 4766-4722.

Vallo CI, Montemartini PE, Cuadrado TR. Effect of residual monomer content on some properties of a poly (methyl methacrylate)‐based bone cement. J Appl Polym Sci. 1998; 69: 1367-1383.

Choi SS, Kim YK. Analysis of Residual Monomers in Poly(acrylonitrile-co-butadiene-co-styrene). Macromol Res. 2012; 20: 585-589.

Kemmere M, van Schilt M, Cleven M, van Herk A, Keurentjes J. Reduction of residual monomer in latex products by enhanced polymerization and extraction in supercritical carbon dioxide. Ind Eng Chem Res. 2002; 41: 2617-2622.

Araújo PHH, Sayer C, Giudici R, Poco JGR. Techniques for reducing residual monomer content in polymers: A review. Polym Eng Sci. 2002; 42: 1442-1468.

Pemberton MA, Lohmann BS. Risk Assessment of residual monomer migrating from acrylic polymers and causing Allergic Contact Dermatitis during normal handling and use. Regul Toxicol Pharmacol. 2014; 69: 467-475.

National Center for Biotechnology Information. https://pubchem.ncbi.nlm.nih.gov/compound/16637#section=Toxicity. Accessed October 7, 2019.

Shekhar S, Mukherjee M, Sen AK. Studies on thermal and swelling properties of Poly(NIPAM-co-2-HEA) based hydrogels. Adv Mat Res. 2012; 1:269-284.

Zhang XZ, Yang YY, Wang FJ, Chung TS. Thermosensitive poly(N-isopropylacrylamide-co-acrylic acid) hydrogels with expanded network structures and improved oscillating swelling–deswelling properties. Langmuir. 2002; 18: 2013-2018.




DOI: https://doi.org/10.2298/HEMIND190717007U

Copyright (c) 2020 HEMIJSKA INDUSTRIJA

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.