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Swelling and diffusion behaviour of spherical morphological polymeric hydrogel membranes (SMPHMs) containing epoxy groups and their application as drug release systems

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Abstract

The aim of the study is to characterize synthesized spherical morphological polymeric hydrogel membranes (SMPHMs), especially their swelling properties, and to show the usability of these SMPHMs in the biomedical applications such as drug delivery systems. Insulin used in the treatment of diabetes mellitus disease was chosen as a model drug to demonstrate the usability of these SMPHMs as a drug delivery system. For this purpose, poly(hydroxyethyl methacrylate-co-glycidyl methacrylate) [P(HEMA-GMA)] SMPHMs were prepared by photopolymerization technique using different monomers mole ratios. Characterization of SMPHMs was carried out with SEM and FTIR analyses. Swelling experiments were conducted in water. Equilibrium percentage swelling values of SMPHMs were calculated and found as in the range of 40–122%, depending on hydrophilic structure of SMPHMs. Swelling kinetic parameters were determined, and the diffusion behaviour of water was also investigated. Water diffusion into the SMPHMs was found to shift from non-Fickian diffusion to Fickian diffusion when HEMA/GMA mole ratio was decreased in the structure of SMPHMs. In the final part of study, insulin release conditions from SMPHMs were optimized. For this purpose, insulin release studies were carried out to investigate the effect of monomer ratios, pH, temperature, and initial insulin concentration. The amount of maximum cumulative insulin release was found as 3747.73 µg/g in pH 7.4, at 25 °C, in the 0.5 mg/mL insulin concentration from SMPHMs-3 in seven hours. According to these obtained results, these SMPHMs can be used as alternative systems for biotechnological applications such as swelling-controlled drug delivery systems.

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References

  1. Peppas NA (1997) Hydrogels and drug delivery. Curr Opin Colloid Interface Sci 2:531–537. https://doi.org/10.1016/S1359-0294(97)80103-3

    Article  CAS  Google Scholar 

  2. Das D, Prakash P, Rout PK, Bhaladhare S (2021) Synthesis and characterization of superabsorbent cellulose-based hydrogel for agriculture application. Starch - Stärke 73:1900284. https://doi.org/10.1002/star.201900284

    Article  CAS  Google Scholar 

  3. Lin C-C, Metters AT (2006) Hydrogels in controlled release formulations: network design and mathematical modeling. Adv Drug Deliv Rev 58:1379–1408. https://doi.org/10.1016/j.addr.2006.09.004

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  5. Deligkaris K, Tadele TS, Olthuis W, van den Berg A (2010) Hydrogel-based devices for biomedical applications. Sens Actuators, B Chem 147:765–774

    Article  CAS  Google Scholar 

  6. Byrne ME, Park K, Peppas NA (2002) Molecular imprinting within hydrogels. Adv Drug Deliv Rev 54:149–161

    Article  CAS  PubMed  Google Scholar 

  7. Hoffman AS (2012) Hydrogels for biomedical applications. Adv Drug Deliv Rev 64:18–23

    Article  Google Scholar 

  8. Wichterle O, Lím D (1960) Hydrophilic gels for biological use. Nature 185:117–118

    Article  Google Scholar 

  9. Ayhan F, Ozkan S (2007) Gentamicin release from photopolymerized PEG diacrylate and pHEMA hydrogel discs and their in vitro antimicrobial activities. Drug Deliv 14:433–439. https://doi.org/10.1080/10717540701202911

    Article  CAS  PubMed  Google Scholar 

  10. Akgöl S, Bayramoğlu G, Kacar Y et al (2002) Poly(hydroxyethyl methacrylate-co-glycidyl methacrylate) reactive membrane utilised for cholesterol oxidase immobilisation. Polym Int 51:1316–1322. https://doi.org/10.1002/pi.875

    Article  CAS  Google Scholar 

  11. Arıca MY, Bayramoğlu G (2004) Polyethyleneimine-grafted poly(hydroxyethyl methacrylate-co-glycidyl methacrylate) membranes for reversible glucose oxidase immobilization. Biochem Eng J 20:73–77. https://doi.org/10.1016/j.bej.2004.04.008

    Article  CAS  Google Scholar 

  12. Kazım K, Akveran GA, Kadir E, Köse DA (2018) Nicotinamide-modified poly (HEMA-GMA)-Nic cryogels for removal of pesticides. J Turkish Chem Soc Sect A Chem 5:941–952

    Article  Google Scholar 

  13. Bayraktaroğlu M, Husein İ, Aktaş Uygun D, Uygun M (2020) Lectin-modified cryogels for laccase immobilization: a decolorization study. Water, Air, Soil Pollut 231:31. https://doi.org/10.1007/s11270-020-4395-3

    Article  CAS  Google Scholar 

  14. Bayramoglu G, Arica MY (2020) Modification of epoxy groups of poly(hydroxylmethyl methacrylate-co-glycidyl methacrylate) cryogel with H3PO4 as adsorbent for removal of hazardous pollutants. Environ Sci Pollut Res 27:43340–43358. https://doi.org/10.1007/s11356-020-10170-y

    Article  CAS  Google Scholar 

  15. Bayramoglu G, Yakup Arica M (2021) Strong and weak cation-exchange groups generated cryogels films for adsorption and purification of lysozyme from chicken egg white. Food Chem 342:128295. https://doi.org/10.1016/j.foodchem.2020.128295

    Article  CAS  PubMed  Google Scholar 

  16. Kopeček J (2007) Hydrogel biomaterials: a smart future? Biomaterials 28:5185–5192

    Article  PubMed  PubMed Central  Google Scholar 

  17. Zhang Y, Zhu W, Ding J (2005) Preparation of thermosensitive microgels via suspension polymerization using different temperature protocols. J Biomed Mater Res - Part A 75:342–349

    Article  Google Scholar 

  18. Baroli B (2006) Photopolymerization of biomaterials: Issues and potentialities in drug delivery, tissue engineering, and cell encapsulation applications. J Chem Technol Biotechnol 81:491–499

    Article  CAS  Google Scholar 

  19. Ganji F, Vasheghani-Farahani E (2009) Hydrogels in controlled drug delivery systems. Iran Polym J 18:63–88

    CAS  Google Scholar 

  20. Nicol E (2021) Photopolymerized porous hydrogels. Biomacromol 22:1325–1345. https://doi.org/10.1021/acs.biomac.0c01671

    Article  CAS  Google Scholar 

  21. Bui HL, Nguyen CTV, Lee W-Y et al (2021) Dopamine-initiated photopolymerization for a versatile catechol-functionalized hydrogel. ACS Appl Bio Mater 4:6268–6279. https://doi.org/10.1021/acsabm.1c00564

    Article  CAS  PubMed  Google Scholar 

  22. Kam D, Braner A, Abouzglo A et al (2021) 3D printing of cellulose nanocrystal-loaded hydrogels through rapid fixation by photopolymerization. Langmuir 37:6451–6458. https://doi.org/10.1021/acs.langmuir.1c00553

    Article  CAS  PubMed  Google Scholar 

  23. Mironi-Harpaz I, Wang DY, Venkatraman S, Seliktar D (2012) Photopolymerization of cell-encapsulating hydrogels: crosslinking efficiency versus cytotoxicity. Acta Biomater 8:1838–1848. https://doi.org/10.1016/j.actbio.2011.12.034

    Article  CAS  PubMed  Google Scholar 

  24. Nguyen KT, West JL (2002) Photopolymerizable hydrogels for tissue engineering applications. Biomaterials 23:4307–4314. https://doi.org/10.1016/S0142-9612(02)00175-8

    Article  CAS  PubMed  Google Scholar 

  25. Roberts JJ, Bryant SJ (2013) Comparison of photopolymerizable thiol-ene PEG and acrylate-based PEG hydrogels for cartilage development. Biomaterials 34:9969–9979. https://doi.org/10.1016/j.biomaterials.2013.09.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Joshi P, Breaux S, Naro J et al (2021) Synthesis and characterization of photopolymerizable hydrogels based on poly (ethylene glycol) for biomedical applications. J Appl Polym Sci 138:50489. https://doi.org/10.1002/app.50489

    Article  CAS  Google Scholar 

  27. Shin J, Kang EH, Choi S et al (2021) Tissue-adhesive chondroitin sulfate hydrogel for cartilage reconstruction. ACS Biomater Sci Eng. https://doi.org/10.1021/acsbiomaterials.0c01414

    Article  PubMed  Google Scholar 

  28. Dou Q, Zhang Z, Wang Y et al (2020) Ultrasensitive poly(boric acid) hydrogel-coated quartz crystal microbalance sensor by using UV pressing-assisted polymerization for saliva glucose monitoring. ACS Appl Mater Interfaces 12:34190–34197. https://doi.org/10.1021/acsami.0c08229

    Article  CAS  PubMed  Google Scholar 

  29. Yin R, Tong Z, Yang D, Nie J (2011) Glucose and pH dual-responsive concanavalin A based microhydrogels for insulin delivery. Int J Biol Macromol 49:1137–1142. https://doi.org/10.1016/j.ijbiomac.2011.09.014

    Article  CAS  PubMed  Google Scholar 

  30. Chakroun RW, Sneider A, Anderson CF et al (2020) Supramolecular design of unsymmetric reverse bolaamphiphiles for cell-sensitive hydrogel degradation and drug release. Angew Chemie Int Ed 59:4434–4442. https://doi.org/10.1002/anie.201913087

    Article  CAS  Google Scholar 

  31. Culebras M, Barrett A, Pishnamazi M et al (2021) Wood-derived hydrogels as a platform for drug-release systems. ACS Sustain Chem Eng 9:2515–2522. https://doi.org/10.1021/acssuschemeng.0c08022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Shafique M, Sohail M, Minhas MU et al (2021) Bio-functional hydrogel membranes loaded with chitosan nanoparticles for accelerated wound healing. Int J Biol Macromol 170:207–221. https://doi.org/10.1016/J.IJBIOMAC.2020.12.157

    Article  CAS  PubMed  Google Scholar 

  33. Khaliq T, Sohail M, Minhas MU et al (2022) Self-crosslinked chitosan/κ-carrageenan-based biomimetic membranes to combat diabetic burn wound infections. Int J Biol Macromol 197:157–168. https://doi.org/10.1016/J.IJBIOMAC.2021.12.100

    Article  CAS  PubMed  Google Scholar 

  34. Abdekhodaie MJ, Wu XY (2009) Modeling of a glucose sensitive composite membrane for closed-loop insulin delivery. J Memb Sci 335:21–31. https://doi.org/10.1016/j.memsci.2009.02.029

    Article  CAS  Google Scholar 

  35. Chu L-Y, Li Y, Zhu J-H et al (2004) Control of pore size and permeability of a glucose-responsive gating membrane for insulin delivery. J Control Release 97:43–53. https://doi.org/10.1016/j.jconrel.2004.02.026

    Article  CAS  PubMed  Google Scholar 

  36. Yin L, Ding J, Fei L et al (2008) Beneficial properties for insulin absorption using superporous hydrogel containing interpenetrating polymer network as oral delivery vehicles. Int J Pharm 350:220–229. https://doi.org/10.1016/j.ijpharm.2007.08.051

    Article  CAS  PubMed  Google Scholar 

  37. Wang R, Tian Y, Wang J et al (2021) Biomimetic glucose trigger-insulin release system based on hydrogel loading bidentate β-cyclodextrin. Adv Funct Mater. https://doi.org/10.1002/adfm.202104488

    Article  PubMed  PubMed Central  Google Scholar 

  38. Feki A, Hamdi M, Jaballi I et al (2020) Conception and characterization of a multi-sensitive composite chitosan-red marine alga-polysaccharide hydrogels for insulin controlled-release. Carbohydr Polym 236:116046. https://doi.org/10.1016/J.CARBPOL.2020.116046

    Article  CAS  PubMed  Google Scholar 

  39. Şenay RH, Gökalp SM, Türker E et al (2015) A new morphological approach for removing acid dye from leather waste water: Preparation and characterization of metal-chelated spherical particulated membranes (SPMs). J Environ Manage 151:295–302. https://doi.org/10.1016/j.jenvman.2014.12.046

    Article  CAS  PubMed  Google Scholar 

  40. Demir EF, Özçalışkan E, Karakaş H et al (2018) Synthesis and characterization of albumin imprinted polymeric hydrogel membranes for proteomic studies. J Biomater Sci Polym Ed 29:2218–2236. https://doi.org/10.1080/09205063.2018.1534423

    Article  CAS  PubMed  Google Scholar 

  41. Karadağ E, Bariş Üzüm Ö, Saraydin D (2005) Water uptake in chemically crosslinked poly(acrylamide-co-crotonic acid) hydrogels. Mater Des 26:265–270. https://doi.org/10.1016/j.matdes.2004.07.014

    Article  CAS  Google Scholar 

  42. Sun L, Zhang X, Zheng C et al (2013) A pH gated, glucose-sensitive nanoparticle based on worm-like mesoporous silica for controlled insulin release. J Phys Chem B. https://doi.org/10.1021/jp400442x

    Article  PubMed  PubMed Central  Google Scholar 

  43. Bai Y, Zhang Z, Zhang A et al (2012) Novel thermo- and pH-responsive hydroxypropyl cellulose- and poly (l-glutamic acid)-based microgels for oral insulin controlled release. Carbohydr Polym 89:1207–1214. https://doi.org/10.1016/j.carbpol.2012.03.095

    Article  CAS  PubMed  Google Scholar 

  44. Bayramoǧlu G, Akgöl S, Bulut A et al (2003) Covalent immobilisation of invertase onto a reactive film composed of 2-hydroxyethyl methacrylate and glycidyl methacrylate: properties and application in a continuous flow system. Biochem Eng J 14:117–126. https://doi.org/10.1016/S1369-703X(02)00170-5

    Article  CAS  Google Scholar 

  45. Arica MY, Yilmaz M, Bayramoğlu G (2007) Chitosan-grafted poly(hydroxyethyl methacrylate-co-glycidyl methacrylate) membranes for reversible enzyme immobilization. J Appl Polym Sci 103:3084–3093. https://doi.org/10.1002/app.25466

    Article  CAS  Google Scholar 

  46. Lee SJ, Kim SS, Lee YM (2000) Interpenetrating polymer network hydrogels based on poly(ethylene glycol) macromer and chitosan. Carbohydr Polym 41:197–205. https://doi.org/10.1016/S0144-8617(99)00088-0

    Article  Google Scholar 

  47. Peniche C, Cohen ME, Vázquez B, San Román J (1997) Water sorption of flexible networks based on 2-hydroxyethyl methacrylate-triethylenglycol dimethacrylate copolymers. Polymer (Guildf) 38:5977–5982. https://doi.org/10.1016/S0032-3861(96)01058-0

    Article  CAS  Google Scholar 

  48. Saraydın D, Karadağ E, Işıkver Y et al (2004) The influence of preparation methods on the swelling and network properties of acrylamide hydrogels with crosslinkers. J Macromol Sci Part A 41:419–431. https://doi.org/10.1081/MA-120028476

    Article  CAS  Google Scholar 

  49. Karadağ E, Üzüm ÖB, Saraydın D, Güven O (2006) Swelling characterization of gamma-radiation induced crosslinked acrylamide/maleic acid hydrogels in urea solutions. Mater Des 27:576–584. https://doi.org/10.1016/j.matdes.2004.11.019

    Article  CAS  Google Scholar 

  50. Kundakci S, Üzüm ÖB, Karadağ E (2009) A new composite sorbent for water and dye uptake: highly swollen acrylamide/2-acrylamido-2-methyl-1-propanesulfonic acid/clay hydrogels crosslinked by 1,4-butanediol dimethacrylate. Polym Compos 30:29–37. https://doi.org/10.1002/pc.20524

    Article  CAS  Google Scholar 

  51. Kundakci S, Öğüt HG, Üzüm ÖB, Karadağ E (2012) Swelling characterization and adsorptive features of acrylamide/itaconic acid hydrogels and semi-IPNs for uranyl ions. Polym Plast Technol Eng 51:1550–1561. https://doi.org/10.1080/03602559.2012.716132

    Article  CAS  Google Scholar 

  52. Karadaǧ E, Üzüm ÖB, Saraydin D (2002) Swelling equilibria and dye adsorption studies of chemically crosslinked superabsorbent acrylamide/maleic acid hydrogels. Eur Polym J 38:2133–2141. https://doi.org/10.1016/S0014-3057(02)00117-9

    Article  Google Scholar 

  53. Karadağ E, Nalbantoğlu A, Kundakcı S, Üzüm ÖB (2014) Highly swollen polymer/clay composite sorbent-based AAm/AMPS hydrogels and semi-IPNs composed of carboxymethyl cellulose and montmorillonite and cross-linked by PEGDA. Polym Plast Technol Eng 53:54–64. https://doi.org/10.1080/03602559.2013.843689

    Article  CAS  Google Scholar 

  54. Peppas NA, Franson NM (1983) The swelling interface number as a criterion for prediction of diffusional solute release mechanisms in swellable polymers. J Polym Sci Polym Phys Ed 21:983–997. https://doi.org/10.1002/pol.1983.180210614

    Article  CAS  Google Scholar 

  55. Zhang N, Shen Y, Li X et al (2012) Synthesis and characterization of thermo- and pH-sensitive poly(vinyl alcohol)/poly(N, N-diethylacrylamide-co-itaconic acid) semi-IPN hydrogels. Biomed Mater 7:035014. https://doi.org/10.1088/1748-6041/7/3/035014

    Article  CAS  PubMed  Google Scholar 

  56. Karadağ E, Kundakci S, Barış Üzüm Ö (2009) Water sorption and dye uptake studies of highly swollen AAm/AMPS hydrogels and semi-IPNs with PEG. Polym Plast Technol Eng 48:1217–1229. https://doi.org/10.1080/03602550903159044

    Article  CAS  Google Scholar 

  57. Rasool N, Yasin T, Heng JYY, Akhter Z (2010) Synthesis and characterization of novel pH-, ionic strength and temperature- sensitive hydrogel for insulin delivery. Polymer (Guildf) 51:1687–1693. https://doi.org/10.1016/j.polymer.2010.02.013

    Article  CAS  Google Scholar 

  58. am Ende MT, Peppas NA, (1997) Transport of ionizable drugs and proteins in crosslinked poly(acrylic acid) and poly(acrylic acid-co-2-hydroxyethyl methacrylate) hydrogels. II. Diffusion and release studies. J Control Release 48:47–56. https://doi.org/10.1016/S0168-3659(97)00032-1

    Article  Google Scholar 

  59. Üzüm ÖB, Karadağ E (2012) Behavior of semi IPN hydrogels composed of PEG and AAm/SMA copolymers in swelling and uptake of janus green B from aqueous solutions. J Appl Polym Sci 125:3318–3328. https://doi.org/10.1002/app.36586

    Article  CAS  Google Scholar 

  60. Karadağ E, Yel B, Kundakcı S, Üzüm ÖB (2020) Water sorption behaviors of novel biohybrid hydrogels as effective sorbents in water-solvent binary mixtures. J Encapsul Adsorpt Sci. https://doi.org/10.4236/jeas.2020.103003

    Article  Google Scholar 

  61. Gao X, He C, Xiao C et al (2013) Biodegradable pH-responsive polyacrylic acid derivative hydrogels with tunable swelling behavior for oral delivery of insulin. Polymer (Guildf) 54:1786–1793. https://doi.org/10.1016/J.POLYMER.2013.01.050

    Article  CAS  Google Scholar 

  62. Park CW, Yang H-M, Lee HJ, Kim J-D (2013) Core–shell nanogel of PEG–poly(aspartic acid) and its pH-responsive release of rh-insulin. Soft Matter. https://doi.org/10.1039/c2sm26865e

    Article  PubMed  PubMed Central  Google Scholar 

  63. Kalaycioglu GD, Elamin AA, Kinali H, Aydogan N (2021) pH-sensitive polymeric poly (ϵ-caprolactone) core- chitosan/alginate shell particle system for oral insulin delivery. ChemistrySelect 6:695–704. https://doi.org/10.1002/slct.202004210

    Article  CAS  Google Scholar 

  64. Wu J-Z, Williams GR, Li H-Y et al (2017) Glucose- and temperature-sensitive nanoparticles for insulin delivery. Int J Nanomed 12:4037–4057. https://doi.org/10.2147/IJN.S132984

    Article  CAS  Google Scholar 

  65. Sun L, Zhang X, Zheng C et al (2012) Glucose- and temperature-responsive core–shell microgels for controlled insulin release. RSC Adv 2:9904. https://doi.org/10.1039/c2ra21408c

    Article  CAS  Google Scholar 

  66. Kumar A, Thakur P, Kumar A (2021) In vitro evaluation of insulin release from chitosan-alginate macrobeads. J Pharm Innov 1–9

  67. Yakup Arıca M, Yilmaz M, Bayramoğlu G (2007) Chitosan-grafted poly(hydroxyethyl methacrylate-co-glycidyl methacrylate) membranes for reversible enzyme immobilization. J Appl Polym Sci 103:3084–3093. https://doi.org/10.1002/app.25466

    Article  CAS  Google Scholar 

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Funding

This study was supported by the Ege University Research Foundation with project no 12 FEN 030.

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Authors and Affiliations

  1. Department of Medical Laboratory Techniques, Vocational School of Health Services, Izmir University of Economics, Izmir, Turkey

    Esra Feyzioğlu-Demir

  2. Department of Chemistry, Faculty of Science and Art, Adnan Menderes University, Aydın, Turkey

    Ömer Barış Üzüm

  3. Department of Biochemistry, Faculty of Science, Ege University, Izmir, Turkey

    Sinan Akgöl

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  1. Esra Feyzioğlu-Demir
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Feyzioğlu-Demir, E., Üzüm, Ö.B. & Akgöl, S. Swelling and diffusion behaviour of spherical morphological polymeric hydrogel membranes (SMPHMs) containing epoxy groups and their application as drug release systems. Polym. Bull. 80, 6567–6590 (2023). https://doi.org/10.1007/s00289-022-04368-y

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