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Investigation of use in 5-FU release: Synthesis of temperature and pH responsive P(NVCL-co-VIm)/PVP hydrogels

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Abstract

5-fluorouracil (5-FU) forms the basis of many chemotherapy regimens and is one of the most common preferred chemotherapeutic drugs. In this study, the synthesis of temperature and pH responsive hydrogels in the release of 5-fluorouracil (5-FU) was studied to prevent drug release during blood circulation and uncontrolled overdose drug concentration at the tumor site. In this regard, the synthesis of temperature sensitive polymer Poly(N-vinylcaprolactam) PNVCL, temperature and pH sensitive polymers P(NVCL-co-VIm) and P(NVCL-co-VIm)/PVP hydrogels was carried out by the free radical polymerization method. DSC analysis revealed that as a result of copolymerization of PNVCL with hydrophilic 1-vinylimidazole (VIm) and polyvinylpyrrolidone (PVP), the lower critical solution temperature (LCST) increased and was close to the human body temperature. In addition, it was concluded from pH sensitivity analysis that the swelling ratios of the hydrogels changed with the medium pH. Additionally, hydrogels swelled in the acidic medium but shrunk in the alkaline medium. Accordingly, 5-FU release was investigated in different temperatures (25 °C and 37 °C) and pH (pH 5.5 and 7.4) medium and approximately 96% drug release was reached at 37 °C and pH 7.4. Consequently, P(NVCL-co-VIm)/PVP hydrogels at different pH and temperature mediums could be beneficially utilized as a material with the potential to be used in targeted drug delivery systems.

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References

  1. Hanahan D, Weinberg RA (2000) The Hallmarks of cancer review evolve progressively from normalcy via a series of pre. Cell 100:57–70

    Article  CAS  PubMed  Google Scholar 

  2. Zugazagoitia J, Guedes C, Ponce S et al (2016) Current challenges in cancer treatment. Clin Ther 38:1551–1566. https://doi.org/10.1016/j.clinthera.2016.03.026

    Article  PubMed  Google Scholar 

  3. Chabner BA, Roberts TG (2005) Chemotherapy and the war on cancer. Nat Rev Cancer 5:65–72. https://doi.org/10.1038/nrc1529

    Article  CAS  PubMed  Google Scholar 

  4. Mitchison DA (1979) Basic mechanisms of chemotherapy. Chest 76:771–780. https://doi.org/10.1378/chest.76.6.771

    Article  CAS  PubMed  Google Scholar 

  5. Wang Z, Mo H, He Z et al (2022) Extracellular vesicles as an emerging drug delivery system for cancer treatment: current strategies and recent advances. Biomed Pharmacother 153:113480. https://doi.org/10.1016/J.BIOPHA.2022.113480

    Article  CAS  PubMed  Google Scholar 

  6. Epstein JB, Thariat J, Bensadoun R-J et al (2012) Oral complications of cancer and cancer therapy. CA Cancer J Clin 62:400–422. https://doi.org/10.3322/CAAC.21157

    Article  PubMed  Google Scholar 

  7. Baudino T (2015) Targeted cancer therapy: the next generation of cancer treatment. Curr Drug Discov Technol 12:3–20. https://doi.org/10.2174/1570163812666150602144310

    Article  CAS  PubMed  Google Scholar 

  8. Giordano S, Petrelli A (2008) From single-to multi-target drugs in cancer therapy: when aspecificity becomes an advantage. Curr Med Chem 15:422–432. https://doi.org/10.2174/092986708783503212

    Article  PubMed  Google Scholar 

  9. Vasir JK, Labhasetwar V (2005) Targeted drug delivery in cancer therapy. Technol Cancer Res Treat 4:363–374. https://doi.org/10.1177/153303460500400405

    Article  CAS  PubMed  Google Scholar 

  10. Chang D, Ma Y, Xu X et al (2021) Stimuli-responsive polymeric nanoplatforms for cancer therapy. Front Bioeng Biotechnol 9:528. https://doi.org/10.3389/FBIOE.2021.707319/BIBTEX

    Article  Google Scholar 

  11. Cheng W, Gu L, Ren W, Liu Y (2014) Stimuli-responsive polymers for anti-cancer drug delivery. Mater Sci Eng C 45:600–608. https://doi.org/10.1016/J.MSEC.2014.05.050

    Article  CAS  Google Scholar 

  12. Gil ES, Hudson SM (2004) Stimuli-reponsive polymers and their bioconjugates. Prog Polym Sci 29:1173–1222. https://doi.org/10.1016/J.PROGPOLYMSCI.2004.08.003

    Article  CAS  Google Scholar 

  13. Bajpai AK, Shukla SK, Bhanu S, Kankane S (2008) Responsive polymers in controlled drug delivery. Prog Polym Sci 33:1088–1118. https://doi.org/10.1016/j.progpolymsci.2008.07.005

    Article  CAS  Google Scholar 

  14. Bawa P, Pillay V, Choonara YE, Du Toit LC (2009) Stimuli-responsive polymers and their applications in drug delivery. Biomed Mater. https://doi.org/10.1088/1748-6041/4/2/022001

    Article  PubMed  Google Scholar 

  15. Aguilar MR, San Román J (eds) (2019) Smart polymers and their applications. Woodhead publishing

  16. Fogueri L, Singh S (2009) Smart polymers for controlled delivery of proteins and peptides: a review of patents. Recent Pat Drug Deliv Formul 3:40–48. https://doi.org/10.2174/187221109787158300

    Article  CAS  PubMed  Google Scholar 

  17. Park IK, Singha K, Arote RB et al (2010) PH-responsive polymers as gene carriers. Macromol Rapid Commun 31:1122–1133

    Article  CAS  PubMed  Google Scholar 

  18. Qureshi D, Nayak SK, Maji S et al (2019) Environment sensitive hydrogels for drug delivery applications. Eur Polym J 120:109220. https://doi.org/10.1016/j.eurpolymj.2019.109220

    Article  CAS  Google Scholar 

  19. Schild HG (1992) Poly(N-isopropylacrylamide): experiment, theory and application. Prog Polym Sci 17:163–249. https://doi.org/10.1016/0079-6700(92)90023-R

    Article  CAS  Google Scholar 

  20. Mohammed MN, Bin Yusoh K, Shariffuddin JHBH (2018) Poly(N-vinyl caprolactam) thermoresponsive polymer in novel drug delivery systems: a review. Mater Express 8:21–34. https://doi.org/10.1166/mex.2018.1406

    Article  CAS  Google Scholar 

  21. Voycheva C, Slavkova M, Popova T et al (2022) Synthesis and characterization of PnVCL grafted agar with potential temperature-sensitive delivery of Doxorubicin. J Drug Deliv Sci Technol 76:103725. https://doi.org/10.1016/J.JDDST.2022.103725

    Article  CAS  Google Scholar 

  22. Edson JA, Kwon YJ (2016) Design, challenge, and promise of stimuli-responsive nanoantibiotics. Nano Converg 3:1–13. https://doi.org/10.1186/S40580-016-0085-7

    Article  Google Scholar 

  23. Sahebi H, Pourmortazavi SM, Zandavar H, Mirsadeghi S (2019) Chitosan grafted onto Fe3O4@poly(N-vinylcaprolactam) as a new sorbent for detecting Imatinib mesylate in biosamples using UPLC-MS/MS. Analyst 144:7336–7350. https://doi.org/10.1039/C9AN01654F

    Article  CAS  PubMed  Google Scholar 

  24. Schmaljohann D (2006) Thermo-and pH-responsive polymers in drug delivery. Adv Drug Deliv Rev 58:1655–1670

    Article  CAS  PubMed  Google Scholar 

  25. Kalhapure RS, Renukuntla J (2018) Thermo-and pH dual responsive polymeric micelles and nanoparticles. Chem Biol Interact 295:20–37. https://doi.org/10.1016/J.CBI.2018.07.016

    Article  CAS  PubMed  Google Scholar 

  26. Anderson EB, Long TE (2010) Imidazole- and imidazolium-containing polymers for biology and material science applications. Polymer 51:2447–2454

    Article  CAS  Google Scholar 

  27. Zhang L, Peng XM, Damu GLV et al (2014) Comprehensive Review in current developments of imidazole-based medicinal chemistry. Med Res Rev 34:340–437. https://doi.org/10.1002/med.21290

    Article  CAS  PubMed  Google Scholar 

  28. Güngör A, Demir D, Bölgen N et al (2021) Dual stimuli-responsive chitosan grafted poly(NIPAM-co-AAc)/poly(vinyl alcohol) hydrogels for drug delivery applications. Int J Polym Mater Polym Biomater 70:810–819. https://doi.org/10.1080/00914037.2020.1765355

    Article  CAS  Google Scholar 

  29. Işik B (2003) Thermoresponsive poly(N-isopropylacrylamide-co-N-vinylimidazole) hydrogels by redox polymerization. Adv Polym Technol 22:246–251. https://doi.org/10.1002/adv.10053

    Article  CAS  Google Scholar 

  30. Yıldız B, Işık B, Kış M (2002) Synthesis and characterization of thermoresponsive isopropylacrylamide–acrylamide hydrogels. Eur Polym J 38(7):1343–1347. https://doi.org/10.1016/S0014-3057(01)00308-1

  31. Işik B, Doǧantekin B (2005) Swelling behavior of poly(acrylamide-co-N-vinylimidazole) hydrogels under different environment conditions. J Appl Polym Sci 96:1783–1788. https://doi.org/10.1002/app.21608

    Article  CAS  Google Scholar 

  32. Carneiro HCF, Tonon RV, Grosso CRF, Hubinger MD (2013) Encapsulation efficiency and oxidative stability of flaxseed oil microencapsulated by spray drying using different combinations of wall materials. J Food Eng 115:443–451. https://doi.org/10.1016/J.JFOODENG.2012.03.033

    Article  CAS  Google Scholar 

  33. Güngör A, Özdemir T, Genç R (2023) Controlled 5-FU release from P(NIPAM-co-VIm)-g-PEG dual responsive hydrogels. ChemistrySelect. https://doi.org/10.1002/SLCT.202203522

    Article  Google Scholar 

  34. Işik B (2004) Swelling behavior and determination of diffusion characteristics of acrylamide-acrylic acid hydrogels. J Appl Polym Sci 91:1289–1293. https://doi.org/10.1002/app.13270

    Article  CAS  Google Scholar 

  35. Park H, Guo X, Temenoff JS et al (2009) Effect of swelling ratio of injectable hydrogel composites on chondrogenic differentiation of encapsulated rabbit marrow mesenchymal stem cells in vitro. Biomacromol 10:541–546. https://doi.org/10.1021/BM801197M/ASSET/IMAGES/LARGE/BM-2008-01197M_0006.JPEG

    Article  CAS  Google Scholar 

  36. Pourjavadi A, Sadeghi M, Hashemi MM, Hosseinzadeh H (2006) Synthesis and absorbency of gelatin-graft-poly(sodium acrylate-co- acrylamide) superabsorbent hydrogel with saltand pH-responsiveness properties. E-Polymers. https://doi.org/10.1515/epoly.2006.6.1.728

    Article  Google Scholar 

  37. Xiao XC (2007) Effect of the initiator on thermosensitive rate of poly(N-isopropylacrylamide) hydrogels. Express Polym Lett 1:232–235. https://doi.org/10.3144/expresspolymlett.2007.35

    Article  CAS  Google Scholar 

  38. Khan S, Ranjha NM (2014) Effect of degree of cross-linking on swelling and on drug release of low viscous chitosan/poly(vinyl alcohol) hydrogels. Polym Bull 71:2133–2158. https://doi.org/10.1007/s00289-014-1178-2

    Article  CAS  Google Scholar 

  39. Bennour S, Louzri F (2014) Study of swelling properties and thermal behavior of poly(N, N-dimethylacrylamide- co -maleic acid) based hydrogels. Adv Chem 2014:1–10. https://doi.org/10.1155/2014/147398

    Article  CAS  Google Scholar 

  40. Chavda H, Patel C (2011) Effect of crosslinker concentration on characteristics of superporous hydrogel. Int J Pharm Investig 1:17. https://doi.org/10.4103/2230-973X.76724

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Śliwa T, Jarzębski M, Andrzejewska E et al (2017) Uptake and controlled release of a dye from thermo-sensitive polymer P(NIPAM-co-Vim). React Funct Polym 115:102–108. https://doi.org/10.1016/j.reactfunctpolym.2017.04.003

    Article  CAS  Google Scholar 

  42. Muratalin M, Luckham PF, Esimova A et al (2017) Study of N-isopropylacrylamide-based microgel particles as a potential drug delivery agents. Colloids Surf A Physicochem Eng Asp 532:8–17. https://doi.org/10.1016/j.colsurfa.2017.07.075

    Article  CAS  Google Scholar 

  43. Kadajji VG, Betageri GV (2011) Water soluble polymers for pharmaceutical applications. Polymers 3:1972–2009. https://doi.org/10.3390/POLYM3041972

    Article  CAS  Google Scholar 

  44. Liu L, Bai S, Yang H et al (2016) Controlled release from thermo-sensitive PNVCL-co-MAA electrospun nanofibers: the effects of hydrophilicity/hydrophobicity of a drug. Mater Sci Eng, C 67:581–589. https://doi.org/10.1016/J.MSEC.2016.05.083

    Article  CAS  Google Scholar 

  45. Morfin-Gutierrez A, Sánchez-Orozco JL, García-Cerda LA et al (2021) Synthesis and characterization of poly(N-vinycaprolactam)-grafted gold nanoparticles by free radical polymerization for using as chemotherapeutic delivery system. Mater Chem Phys 266:124535. https://doi.org/10.1016/J.MATCHEMPHYS.2021.124535

    Article  CAS  Google Scholar 

  46. Chi H, Chen P, Cao L et al (2016) Characterization and adsorptive properties of cross-linked poly (1-vinylimidazole)-iron (III) complex synthesized in supercritical carbon dioxide. E-Polymers 16:403–410. https://doi.org/10.1515/epoly-2016-0096

    Article  CAS  Google Scholar 

  47. Fidalgo A, Ilharco LM (2001) The defect structure of sol–gel-derived silica/polytetrahydrofuran hybrid films by FTIR. J Non Cryst Solids 283:144–154. https://doi.org/10.1016/S0022-3093(01)00418-5

    Article  CAS  Google Scholar 

  48. Alam AKMM, Beg MDH, Yunus RM et al (2021) Tailoring the dispersibility of non-covalent functionalized multi-walled carbon nanotube (MWCNT) nanosuspension using shellac (SL) bio-resin: structure-property relationship and cytotoxicity of shellac coated carbon nanotubes (SLCNTs). Colloid Interface Sci Commun 42:100395. https://doi.org/10.1016/J.COLCOM.2021.100395

    Article  CAS  Google Scholar 

  49. Nouralishahi A, Khodadadi AA, Mortazavi Y et al (2014) Enhanced methanol electro-oxidation activity of Pt/MWCNTs electro-catalyst using manganese oxide deposited on MWCNTs. Electrochim Acta 147:192–200. https://doi.org/10.1016/J.ELECTACTA.2014.09.113

    Article  CAS  Google Scholar 

  50. Alam AKMM, Beg MDH, Yunus RM et al (2016) Evolution of functionalized multi-walled carbon nanotubes by dendritic polymer coating and their anti-scavenging behavior during curing process. Mater Lett 167:58–60. https://doi.org/10.1016/J.MATLET.2015.12.130

    Article  Google Scholar 

  51. Kozanoǧlu S, Özdemir T, Usanmaz A (2011) Polymerization of N-vinylcaprolactam and characterization of poly(N-vinylcaprolactam). J Macromol Sci Part A Pure Appl Chem 48:467–477. https://doi.org/10.1080/10601325.2011.573350

    Article  CAS  Google Scholar 

  52. Pino-Ramos VH, Cedillo G, López-Barriguete E, Bucio E (2019) Comonomer effect: switching the lower critical solution temperature to upper critical solution temperature in thermo-pH sensitive binary graft copolymers. J Appl Polym Sci 136:1–9. https://doi.org/10.1002/app.48170

    Article  CAS  Google Scholar 

  53. El Hoshoudy A (2015) Synthesis and characterization of polyacrylamide crosslinked copolymer for enhanced oil recovery and rock wettability alteration. Int J Oil Gas Coal Eng 3:43. https://doi.org/10.11648/j.ogce.20150304.11

    Article  CAS  Google Scholar 

  54. Rahma A, Munir MM, Khairurrijal et al (2016) Intermolecular interactions and the release pattern of electrospun curcumin-polyvinyl(pyrrolidone) fiber. Biol Pharm Bull 39:163–173. https://doi.org/10.1248/bpb.b15-00391

    Article  CAS  PubMed  Google Scholar 

  55. Osman Z, Arof AK (2003) FTIR studies of chitosan acetate based polymer electrolytes. Electrochim Acta 48:993–999. https://doi.org/10.1016/S0013-4686(02)00812-5

    Article  CAS  Google Scholar 

  56. Pasparakis G, Tsitsilianis C (2020) LCST polymers: thermoresponsive nanostructured assemblies towards bioapplications. Polymer 211:123146. https://doi.org/10.1016/J.POLYMER.2020.123146

    Article  CAS  Google Scholar 

  57. Horta A, Molina MJ, Gómez-Antón MR, Piérola IF (2009) The pH inside a pH-sensitive gel swollen in aqueous salt solutions: poly(N-vinylimidazole). Macromolecules 42:1285–1292. https://doi.org/10.1021/MA802204B/ASSET/IMAGES/MA-2008-02204B_M026.GIF

    Article  CAS  Google Scholar 

  58. Horta A, Piérola IF (2009) Poly(N-vinylimidazole) gels as insoluble buffers that neutralize acid solutions without dissolving. J Phys Chem B 113:4226–4231. https://doi.org/10.1021/JP809682D/ASSET/IMAGES/JP-2008-09682D_M024.GIF

    Article  CAS  PubMed  Google Scholar 

  59. Longley DB, Harkin DP, Johnston PG (2003) 5-Fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 3:330–338. https://doi.org/10.1038/nrc1074

    Article  CAS  PubMed  Google Scholar 

  60. Masaki M, Ogawa K, Kokufuta E (2009) Unusual behavior in light scattering experiments of poly(N-vinylimidazole) prepared by precipitation polymerization. Colloid Polym Sci 287:1405–1415. https://doi.org/10.1007/S00396-009-2104-2/FIGURES/8

    Article  CAS  Google Scholar 

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Acknowledgements

This study was supported by the Mersin University Scientific Research Projects Department [Project number 2018-1-TP3-2842].

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Authors and Affiliations

  1. Faculty of Engineering and Natural Sciences, Sabancı University, Orhanlı, 34956, Tuzla, İstanbul, Turkey

    Ahmet Güngör

  2. Department of Chemical Engineering, Faculty of Engineering, Mersin University, 33343, Yenişehir, Mersin, Turkey

    Tonguç Özdemir & Rükan Genç

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  1. Ahmet Güngör
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Güngör, A., Özdemir, T. & Genç, R. Investigation of use in 5-FU release: Synthesis of temperature and pH responsive P(NVCL-co-VIm)/PVP hydrogels. Polym. Bull. 81, 2091–2109 (2024). https://doi.org/10.1007/s00289-023-04806-5

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