Fabrication of Interpenetrating Polymer Network-Based Hydrogel for Colon-Targeted Release of Nateglinide
DOI:
https://doi.org/10.35516/jjps.v16i4.775Keywords:
Chitosan-Poly(meth(methacrylic)) Acid hydrogel, Interpenetrating Polymer Network, Nateglinide, Biodegradable, pH-SensitiveAbstract
Nateglinide is an anti-diabetic agent that experiences modest first-pass metabolism and poor aqueous solubility. This paper explores the preparation, characterization, and evaluation of interpenetrating polymer network composite hydrogels of chitosan and poly(meth(methacrylic)) acid as a potential carrier for the drug. Interpenetrating polymer network composite hydrogels of chitosan and poly(meth(methacrylic) acid incorporating nateglinide were prepared using N,Nꞌ-methylene bisacrylamide and glutaraldehyde as cross-linkers. The polymerization of chitosan, entrapment of the drug, and its interaction in prepared hydrogels were checked by FTIR spectroscopy, DSC, and powder XRD studies. The hydrogels were evaluated for their swelling behavior and in vitro drug release. The morphology of the hydrogels before and after dissolution was studied using SEM. The hydrogels showed a 93.29 ± 4.65% yield and 91.28 ± 2.22% drug loading. The hydrogels exhibited pH-sensitive swelling behavior. The in vitro release profile confirmed that the drug release depended on the swelling of hydrogels and showed a biphasic release pattern. Chitosan-poly(meth(methacrylic)) acid interpenetrating polymer network hydrogel, with its biodegradable nature and pH-sensitive release of nateglinide, is an attractive option to be further explored for targeted controlled drug delivery formulations for the drug.
References
Tentolouris N, Voulgari C, Katsilambros N. A review of nateglinide in the management of patients with type 2 diabetes. Vasc Health Risk Manag. 2007; 3(6): 797-807.
Wairkar S, Gaud R, Jadhav N. Enhanced dissolution and bioavailability of Nateglinide by microenvironmental pH-regulated ternary solid dispersion: in-vitro and in-vivo evaluation. J Pharm Pharmacol. 2017; 69(9): 1099-1109. https://doi.org/10.1111/jphp.12756 DOI: https://doi.org/10.1111/jphp.12756
Sahoo RK, Biswas N, Guha A, Sahoo N, Kuotsu K. Development and in vitro/in vivo evaluation of controlled release provesicles of a nateglinide-maltodextrin complex. Acta Pharm Sin B. 2014; 4(5): 408-416. https://doi.org/10.1016/j.apsb.2014.08.001 DOI: https://doi.org/10.1016/j.apsb.2014.08.001
Vinod M, Jitendra N, Komal P, Rahul C, Gokul K. Enhancement of Solubility with Formulation & in-vitro Evaluation of Oral Nateglinide Compacts by Liquisolid Technique. Advances in Diabetes and Metabolism. 2013; 1(3): 57-64. https://doi.org/10.13189/adm.2013.010302 DOI: https://doi.org/10.13189/adm.2013.010302
Terada T, Sawada K, Saito H, Hashimoto Y, Inui K. Inhibitory effect of novel oral hypoglycemic agent nateglinide (AY4166) on peptide transporters PEPT1 and PEPT2. Eur J Pharmacol. 2000; 392(1-2): 11-17. https://doi.org/10.1016/s0014-2999(00)00119-9 DOI: https://doi.org/10.1016/S0014-2999(00)00119-9
Keilson L, Mather S, Walter YH, Subramanian S, McLeod JF. Synergistic effects of nateglinide and meal administration on insulin secretion in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2000; 85(3): 1081-1086. https://doi.org/10.1210/jcem.85.3.6446 DOI: https://doi.org/10.1210/jcem.85.3.6446
Guardado-Mendoza R, Prioletta A, Jiménez-Ceja LM, Sosale A, Folli F. The role of nateglinide and repaglinide, derivatives of meglitinide, in the treatment of type 2 diabetes mellitus. Arch Med Sci. 2013; 9(5): 936-943. https://doi.org/10.5114/aoms.2013.34991 DOI: https://doi.org/10.5114/aoms.2013.34991
Devineni D, Walter YH, Smith HT, Lee JS, Prasad P, McLeod JF. Pharmacokinetics of Nateglinide in Renally Impaired Diabetic Patients. The Journal of Clinical Pharmacology. 2003; 43(2): 163-170.
https://doi.org/10.1177/0091270002239825 DOI: https://doi.org/10.1177/0091270002239825
Aylsworth JW. Plastic composition. Published online September 22, 1914. Accessed February 8, 2022. https: //patents.google.com/patent/US1111284A/en
Lohani A, Singh G, Bhattacharya SS, Verma A. Interpenetrating Polymer Networks as Innovative Drug Delivery Systems. Journal of Drug Delivery. 2014; 2014: 1-11. https://doi.org/10.1155/2014/583612 DOI: https://doi.org/10.1155/2014/583612
Kulkarni RV, Sreedhar V, Mutalik S, Setty CM, Sa B. Interpenetrating network hydrogel membranes of sodium alginate and poly(vinyl alcohol) for controlled release of prazosin hydrochloride through skin. International Journal of Biological Macromolecules. 2010; 47(4): 520-527. https://doi.org/10.1016/j.ijbiomac.2010.07.009 DOI: https://doi.org/10.1016/j.ijbiomac.2010.07.009
Xu Q, Huang W, Jiang L, Lei Z, Li X, Deng H. KGM and PMAA based pH-sensitive interpenetrating polymer network hydrogel for controlled drug release. Carbohydrate Polymers. 2013; 97(2): 565-570. https://doi.org/10.1016/j.carbpol.2013.05.007 DOI: https://doi.org/10.1016/j.carbpol.2013.05.007
Boppana R, Kulkarni RV, Mutalik SS, Setty CM, Sa B. Interpenetrating network hydrogel beads of carboxymethylcellulose and egg albumin for controlled release of lipid lowering drug. Journal of Microencapsulation. 2010; 27(4): 337-344. https://doi.org/10.3109/02652040903191842 DOI: https://doi.org/10.3109/02652040903191842
Malakar J, Nayak AK, Pal D. Development of cloxacillin loaded multiple-unit alginate-based floating system by emulsion–gelation method. International Journal of Biological Macromolecules. 2012; 50(1): 138-147. https://doi.org/10.1016/j.ijbiomac.2011.10.001 DOI: https://doi.org/10.1016/j.ijbiomac.2011.10.001
Kumar P, Pillay V, Choonara YE. Macroporous chitosan/methoxypoly (ethylene glycol) based cryosponges with unique morphology for tissue engineering applications. Sci Rep. 2021; 11(1): 3104. https://doi.org/10.1038/s41598-021-82484-x DOI: https://doi.org/10.1038/s41598-021-82484-x
Kondolot Solak E, Er A. pH-sensitive interpenetrating polymer network microspheres of poly(vinyl alcohol) and carboxymethyl cellulose for controlled release of the nonsteroidal anti-inflammatory drug ketorolac tromethamine. Artificial Cells, Nanomedicine, and Biotechnology. 2016; 44(3): 817-824.
https://doi.org/10.3109/21691401.2014.982805 DOI: https://doi.org/10.3109/21691401.2014.982805
Nita LE, Chiriac AP, Rusu AG, et al. Stimuli Responsive Scaffolds Based on Carboxymethyl Starch and Poly(2-Dimethylaminoethyl Methacrylate) for Anti-Inflammatory Drug Delivery. Macromol Biosci. 2020; 20(4): e1900412.
https://doi.org/10.1002/mabi.201900412 DOI: https://doi.org/10.1002/mabi.201900412
Boschetti PJ, Toro DJ, Ontiveros A, Pelliccioni O, Sabino MA. Lattice Boltzmann method simulations of swelling of cuboid-shaped IPN hydrogel tablets with experimental validation. Heat Mass Transfer. Published online October 10, 2021. https://doi.org/10.1007/s00231-021-03132-8 DOI: https://doi.org/10.1007/s00231-021-03132-8
Dai Z, Yang X, Wu F, et al. Living fabrication of functional semi-interpenetrating polymeric materials. Nat Commun. 2021; 12(1): 3422.
https://doi.org/10.1038/s41467-021-23812-7 DOI: https://doi.org/10.1038/s41467-021-23812-7
Hasan MdM, Chisty AH, Rahman MM, Khan MN. Bioprotein Based IPN Nanoparticles as Potential Vehicles for Anticancer Drug Delivery: Fabrication Technology. In: Jana S, Jana S, eds. Interpenetrating Polymer Network: Biomedical Applications. Springer; 2020: 183-203. https://doi.org/10.1007/978-981-15-0283-5_7 DOI: https://doi.org/10.1007/978-981-15-0283-5_7
Abou El-Ela RM, Freag MS, Elkhodairy KA, Elzoghby AO. Interpenetrating Polymer Network (IPN) Nanoparticles for Drug Delivery Applications. In: Jana S, Jana S, eds. Interpenetrating Polymer Network: Biomedical Applications. Springer; 2020: 25-54. https://doi.org/10.1007/978-981-15-0283-5_2 DOI: https://doi.org/10.1007/978-981-15-0283-5_2
Kadri R, Elkhoury K, Ben Messaoud G, et al. Physicochemical Interactions in Nanofunctionalized Alginate/GelMA IPN Hydrogels. Nanomaterials. 2021; 11(9): 2256. https://doi.org/10.3390/nano11092256 DOI: https://doi.org/10.3390/nano11092256
Li S, Shao C, Miao Z, Lu P. Development of leftover rice/gelatin interpenetrating polymer network films for food packaging. Green Processing and Synthesis. 2021; 10(1): 37-48. https://doi.org/10.1515/gps-2021-0004 DOI: https://doi.org/10.1515/gps-2021-0004
Mohammad Gholiha H, Ehsani M, Saeidi A, Ghadami A, Alizadeh N. Magnetic dual-responsive semi-IPN nanogels based on chitosan/PNVCL and study on BSA release behavior. Prog Biomater. 2021; 10(3): 173-183. https://doi.org/10.1007/s40204-021-00161-8 DOI: https://doi.org/10.1007/s40204-021-00161-8
Qin Z, Zhang R, Xu Y, Cao Y, Xiao L. A one-pot synthesis of thermosensitive PNIPAAM interpenetration polymer networks(IPN) hydrogels. JCIS Open. 2021; 1: 100002. https://doi.org/10.1016/j.jciso.2021.100002 DOI: https://doi.org/10.1016/j.jciso.2021.100002
Lim LS, Rosli NA, Ahmad I, Mat Lazim A, Mohd Amin MCI. Synthesis and Swelling Behavior of pH-Sensitive Semi-IPN Superabsorbent Hydrogels Based on Poly(acrylic acid) Reinforced with Cellulose Nanocrystals. Nanomaterials (Basel). 2017; 7(11): E399.
https://doi.org/10.3390/nano7110399 DOI: https://doi.org/10.3390/nano7110399
Dragan ES, Cocarta AI. Smart Macroporous IPN Hydrogels Responsive to pH, Temperature, and Ionic Strength: Synthesis, Characterization, and Evaluation of Controlled Release of Drugs. ACS Appl Mater Interfaces. 2016; 8(19): 12018-12030.
https://doi.org/10.1021/acsami.6b02264 DOI: https://doi.org/10.1021/acsami.6b02264
Sarmad S, Yenici G, Gürkan K, Keçeli G, Gürdağ G. Electric field responsive chitosan–poly(N,N-dimethyl acrylamide) semi-IPN gel films and their dielectric, thermal and swelling characterization. Smart Mater Struct. 2013; 22(5): 055010.
https://doi.org/10.1088/0964-1726/22/5/055010 DOI: https://doi.org/10.1088/0964-1726/22/5/055010
Zhou L, Ma T, Li T, Ma X, Yin J, Jiang X. Dynamic Interpenetrating Polymer Network (IPN) Strategy for Multiresponsive Hierarchical Pattern of Reversible Wrinkle. ACS Appl Mater Interfaces. 2019; 11(17): 15977-15985. https://doi.org/10.1021/acsami.8b22216 DOI: https://doi.org/10.1021/acsami.8b22216
Almasri R, Swed A, Alali H. Preparation and Characterization of Hydrogel Beads for Controlled Release of Amoxicillin. Jordan Journal of Pharmaceutical Sciences. 2022; 15(4): 523-535. https://doi.org/10.35516/jjps.v15i4.675 DOI: https://doi.org/10.35516/jjps.v15i4.675
Ahmed EM. Hydrogel: Preparation, characterization, and applications: A review. Journal of Advanced Research. 2015; 6(2): 105-121.
https://doi.org/10.1016/j.jare.2013.07.006 DOI: https://doi.org/10.1016/j.jare.2013.07.006
Giri TK, Thakur A, Alexander A, Ajazuddin, Badwaik H, Tripathi DK. Modified chitosan hydrogels as drug delivery and tissue engineering systems: present status and applications. Acta Pharmaceutica Sinica B. 2012; 2(5): 439-449. https://doi.org/10.1016/j.apsb.2012.07.004 DOI: https://doi.org/10.1016/j.apsb.2012.07.004
Abudayah AAF. Implication of Nanotechnology for Pulmonary Delivery of Docetaxel. Jordan Journal of Pharmaceutical Sciences. 2023; 16(2): 470-470. https://doi.org/10.35516/jjps.v16i2.1527 DOI: https://doi.org/10.35516/jjps.v16i2.1527
Lee JW, Kim SY, Kim SS, Lee YM, Lee KH, Kim SJ. Synthesis and characteristics of interpenetrating polymer network hydrogel composed of chitosan and poly(acrylic acid). Journal of Applied Polymer Science. 1999; 73(1): 113-120. DOI: https://doi.org/10.1002/(SICI)1097-4628(19990705)73:1<113::AID-APP13>3.0.CO;2-D
https://doi.org/10.1002/(SICI)1097- 4628(19990705)73: 1<113: : AID-APP13>3.0.CO; 2-D
Wang Y, Wang J, Yuan Z, et al. Chitosan cross-linked poly(acrylic acid) hydrogels: Drug release control and mechanism. Colloids and Surfaces B: Biointerfaces. 2017; 152: 252-259.
https://doi.org/10.1016/j.colsurfb.2017.01.008 DOI: https://doi.org/10.1016/j.colsurfb.2017.01.008
Yadav KH, Satish CS, Shivakumar HG. Preparation and evaluation of chitosan-poly (acrylic acid) hydrogels as stomach specific delivery for amoxicillin and metronidazole. Indian Journal of Pharmaceutical Sciences. 2007; 69(1): 91. https://doi.org/10.4103/0250-474X.32115 DOI: https://doi.org/10.4103/0250-474X.32115
Milosavljević NB, Milašinović NZ, Popović IG, Filipović JM, Kalagasidis Krušić MT. Preparation and characterization of pH-sensitive hydrogels based on chitosan, itaconic acid and methacrylic acid: pH-sensitive hydrogels based on Ch, IA and MAA. Polym Int. 2011; 60(3): 443-452. https://doi.org/10.1002/pi.2967 DOI: https://doi.org/10.1002/pi.2967
Yazdani-Pedram M, Retuert J, Quijada R. Hydrogels based on modified chitosan, 1. Synthesis and swelling behavior of poly(acrylic acid) grafted chitosan. Macromolecular Chemistry and Physics. 2000; 201(9): 923-930. DOI: https://doi.org/10.1002/1521-3935(20000601)201:9<923::AID-MACP923>3.0.CO;2-W
https://doi.org/10.1002/1521-3935(20000601)201: 9<923: : AID-MACP923>3.0.CO; 2-W
Wang H, Li W, Lu Y, Wang Z. Studies on chitosan and poly(acrylic acid) interpolymer complex. I. Preparation, structure, pH-sensitivity, and salt sensitivity of complex-forming poly(acrylic acid): Chitosan semi-interpenetrating polymer network. Journal of Applied Polymer Science. 1997; 65(8): 1445-1450. https://doi.org/10.1002/(SICI)1097-4628(19970822)65: 8<1445::AID-APP1>3.0.CO; 2-G DOI: https://doi.org/10.1002/(SICI)1097-4628(19970822)65:8<1445::AID-APP1>3.0.CO;2-G
Fujiwara M, Grubbs RH, Baldeschwieler JD. Characterization of pH-Dependent Poly(acrylic Acid) Complexation with Phospholipid Vesicles. Journal of Colloid and Interface Science. 1997; 185(1): 210-216. https://doi.org/10.1006/jcis.1996.4608 DOI: https://doi.org/10.1006/jcis.1996.4608
Tavakol M, Vasheghani-Farahani E, Dolatabadi-Farahani T, Hashemi-Najafabadi S. Sulfasalazine release from alginate-N,O-carboxymethyl chitosan gel beads coated by chitosan. Carbohydrate Polymers. 2009; 77(2): 326-330. https://doi.org/10.1016/j.carbpol.2009.01.005 DOI: https://doi.org/10.1016/j.carbpol.2009.01.005
Torre P. Release of amoxicillin from polyionic complexes of chitosan and poly(acrylic acid). study of polymer/polymer and polymer/drug interactions within the network structure. Biomaterials. 2003; 24(8): 1499-1506. https://doi.org/10.1016/S0142-9612(02)00512-4 DOI: https://doi.org/10.1016/S0142-9612(02)00512-4
Silva CL, Pereira JC, Ramalho A, Pais AACC, Sousa JJS. Films based on chitosan polyelectrolyte complexes for skin drug delivery: Development and characterization. Journal of Membrane Science. 2008; 320(1-2): 268-279. https://doi.org/10.1016/j.memsci.2008.04.011 DOI: https://doi.org/10.1016/j.memsci.2008.04.011
Helal SH, Abdel-Aziz HMM, El-Zayat MM, Hasaneen MNA. Preparation, characterization and properties of three different nanomaterials either alone or loaded with nystatin or fluconazole antifungals. Sci Rep. 2022; 12(1): 22110. https://doi.org/10.1038/s41598-022-26523-1 DOI: https://doi.org/10.1038/s41598-022-26523-1
Brady J, Dürig T, Lee PI, Li JX. Chapter 7 - Polymer Properties and Characterization. In: Qiu Y, Chen Y, Zhang GGZ, Yu L, Mantri RV, eds. Developing Solid Oral Dosage Forms (Second Edition). Academic Press; 2017: 181-223. https://doi.org/10.1016/B978-0-12-802447-8.00007-8 DOI: https://doi.org/10.1016/B978-0-12-802447-8.00007-8
Hhr C, K C, Ja LP, et al. Design and Optimization of a Nanoparticulate Pore Former as a Multifunctional Coating Excipient for pH Transition-Independent Controlled Release of Weakly Basic Drugs for Oral Drug Delivery. Pharmaceutics. 2023; 15(2).
https://doi.org/10.3390/pharmaceutics15020547 DOI: https://doi.org/10.3390/pharmaceutics15020547
Tian Y, Lei M. Polydopamine-Based Composite Nanoparticles with Redox-Labile Polymer Shells for Controlled Drug Release and Enhanced Chemo-Photothermal Therapy. Nanoscale Res Lett. 2019; 14(1): 186. https://doi.org/10.1186/s11671-019-3027-6 DOI: https://doi.org/10.1186/s11671-019-3027-6
Duarte Junior AP, Tavares EJM, Alves TVG, et al. Chitosan nanoparticles as a modified diclofenac drug release system. J Nanopart Res. 2017; 19(8): 274. https://doi.org/10.1007/s11051-017-3968-6 DOI: https://doi.org/10.1007/s11051-017-3968-6
El-Sherbiny IM. Enhanced pH-responsive carrier system based on alginate and chemically modified carboxymethyl chitosan for oral delivery of protein drugs: Preparation and in-vitro assessment. Carbohydrate Polymers. 2010; 80(4): 1125-1136.
https://doi.org/10.1016/j.carbpol.2010.01.034 DOI: https://doi.org/10.1016/j.carbpol.2010.01.034
de Abreu FR, Campana-Filho SP. Characteristics and properties of carboxymethylchitosan. Carbohydrate Polymers. 2009; 75(2): 214-221.
https://doi.org/10.1016/j.carbpol.2008.06.009 DOI: https://doi.org/10.1016/j.carbpol.2008.06.009
Nam S. Pervaporation and properties of chitosan-poly(acrylic acid) complex membranes. Journal of Membrane Science. 1997; 135(2): 161-171.
https://doi.org/10.1016/S0376-7388(97)00144-0 DOI: https://doi.org/10.1016/S0376-7388(97)00144-0
Risbud MV, Hardikar AA, Bhat SV, Bhonde RR. pH-sensitive freeze-dried chitosan-polyvinyl pyrrolidone hydrogels as controlled release system for antibiotic delivery. J Control Release. 2000; 68(1): 23-30. https://doi.org/10.1016/s0168-3659(00)00208-x DOI: https://doi.org/10.1016/S0168-3659(00)00208-X
Banerjee T, Mitra S, Kumar Singh A, Kumar Sharma R, Maitra A. Preparation, characterization and biodistribution of ultrafine chitosan nanoparticles. International Journal of Pharmaceutics. 2002; 243(1): 93-105. https://doi.org/10.1016/S0378-5173(02)00267-3 DOI: https://doi.org/10.1016/S0378-5173(02)00267-3
Bruni G, Berbenni V, Milanese C, et al. Thermodynamic relationships between nateglinide polymorphs. J Pharm Biomed Anal. 2009; 50(5): 764-770.
https://doi.org/10.1016/j.jpba.2009.06.017 DOI: https://doi.org/10.1016/j.jpba.2009.06.017
Bruni G, Berbenni V, Milanese C, et al. Determination of the nateglinide polymorphic purity through DSC. J Pharm Biomed Anal. 2011; 54(5): 1196-1199.
https://doi.org/10.1016/j.jpba.2010.12.003 DOI: https://doi.org/10.1016/j.jpba.2010.12.003
Neira-Carrillo A, Yazdani-Pedram M, Retuert J, Diaz-Dosque M, Gallois S, Arias JL. Selective crystallization of calcium salts by poly(acrylate)-grafted chitosan. J Colloid Interface Sci. 2005; 286(1): 134-141. https://doi.org/10.1016/j.jcis.2004.12.046
Goyal P, Rani D, Chadha R. Exploring structural aspects of nateglinide polymorphs using powder X-ray diffraction. International Journal of Pharmacy and Pharmaceutical Sciences. Published online October 2, 2017: 119-127.
https://doi.org/10.22159/ijpps.2017v9i10.20795 DOI: https://doi.org/10.22159/ijpps.2017v9i10.20795
El-Sherbiny IM. Synthesis, characterization and metal uptake capacity of a new carboxymethyl chitosan derivative. European Polymer Journal. 2009; 45(1): 199-210. https://doi.org/10.1016/j.eurpolymj.2008.10.042 DOI: https://doi.org/10.1016/j.eurpolymj.2008.10.042
Bauer S, Störmer E, Kirchheiner J, Michael C, Brockmöller J, Roots I. Rapid and simple method for the analysis of nateglinide in human plasma using HPLC analysis with UV detection. J Pharm Biomed Anal. 2003; 31(3): 551-555.
https://doi.org/10.1016/s0731-7085(02)00680-5 DOI: https://doi.org/10.1016/S0731-7085(02)00680-5
Neira-Carrillo A, Yazdani-Pedram M, Retuert J, Diaz-Dosque M, Gallois S, Arias JL. Selective crystallization of calcium salts by poly(acrylate)-grafted chitosan. J Colloid Interface Sci. 2005; 286(1): 134-141. https://doi.org/10.1016/j.jcis.2004.12.046 DOI: https://doi.org/10.1016/j.jcis.2004.12.046
Raj BS, Shanthi, Nair RS, Samraj PI, Vidya. Formulation and Evaluation of Coated Microspheres for Colon Targeting. J App Pharm Sci. 2013; 3(8): S68-S74. https://doi.org/10.7324/JAPS.2013.38.S11 DOI: https://doi.org/10.7324/JAPS.2013.38.S11
Ren Y, Jiang L, Yang S, et al. Design and preparation of a novel colon-targeted tablet of hydrocortisone. Braz J Pharm Sci. 2016; 52: 239-250.
https://doi.org/10.1590/S1984-82502016000200002 DOI: https://doi.org/10.1590/S1984-82502016000200002
Jin L, Ding YC, Zhang Y, Xu XQ, Cao Q. A novel pH-enzyme-dependent mesalamine colon-specific delivery system. Drug Des Devel Ther. 2016; 10: 2021-2028. https://doi.org/10.2147/DDDT.S107283 DOI: https://doi.org/10.2147/DDDT.S107283
Maity S, Kundu A, Karmakar S, Sa B. In Vitro and In Vivo Correlation of Colon-Targeted Compression-Coated Tablets. Journal of Pharmaceutics. 2016; 2016: e5742967. https://doi.org/10.1155/2016/5742967 DOI: https://doi.org/10.1155/2016/5742967
Alfrey Jr. T, Pinner SH. Preparation and titration of amphoteric polyelectrolytes. Journal of Polymer Science. 1957; 23(104): 533-547.
https://doi.org/10.1002/pol.1957.1202310402 DOI: https://doi.org/10.1002/pol.1957.1202310402
