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RETRACTED ARTICLE: Natural Polymer-Based Graphene Oxide Bio-nanocomposite Hydrogel Beads: Superstructures with Advanced Potentials for Drug Delivery

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This article was retracted on 19 March 2024

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Abstract

The current study sought to create graphene oxide-based superstructures for gastrointestinal drug delivery. Graphene oxide has a large surface area that can be used to load anti-cancer drugs via non-covalent methods such as surface adsorption and hydrogen bonding. To enhance the bio-applicability of graphene oxide, nano-hybrids were synthesized by encapsulating the graphene oxide into calcium alginate hydrogel beads through the dripping-extrusion technique. These newly developed bio-nanocomposite hybrid hydrogel beads were evaluated in structural analysis, swelling study, drug release parameters, haemolytic assay, and antibacterial activity. Doxorubicin served as a model drug. The drug entrapment efficiency was determined by UV-spectroscopy analysis and was found to be high at ⁓89% in graphene oxide hybrid hydrogel beads. These fabricated hydrogel beads ensure the drug release from a hybrid polymeric matrix in a more controlled and sustained pattern avoiding the problems associated with a non-hybrid polymeric system. The drug release study of 12 h shows about 83% release at pH 6.8. In vitro drug release kinetics proved that drug release was a Fickian mechanism. The cytotoxic effect of graphene oxide hybrid alginate beads was also determined by evaluating the morphology of bacterial cells and red blood cells after incubation. Additionally, it was determined that the sequential encapsulation of graphene oxide in alginate hydrogel beads hides its uneven edges and lessens the graphene oxide’s negative impacts. Also, the antibacterial study and biocompatibility of fabricated hydrogel beads made them potential candidates for gastrointestinal delivery.

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References

  1. Geim AK, Novoselov KS. The rise of graphene. In: Nanoscience and technology: a collection of reviews from nature journals. World Scientific;  2010; p. 11–19.

  2. Georgakilas V. Functionalization of graphene. John Wiley & Sons. 2014.

  3. Valentini F, Andrea C, Vincenzo R, Di Giacobbe M, Botta M, Talamo M. Graphene as nanocarrier in drug delivery. 2018.

  4. Yang X, et al. High-efficiency loading and controlled release of doxorubicin hydrochloride on graphene oxide. J Phys Chem C. 2008;112(45):17554–8.

    Article  CAS  Google Scholar 

  5. Smith AT, et al. Synthesis, properties, and applications of graphene oxide/reduced graphene oxide and their nanocomposites. Nano Mater Sci. 2019;1(1):31–47.

    Article  Google Scholar 

  6. de Moraes ACM, et al. Graphene oxide-silver nanocomposite as a promising biocidal agent against methicillin-resistant Staphylococcus aureus. Int J Nanomed. 2015;10:6847.

    Article  Google Scholar 

  7. Pourjavadi A, et al. Preparation of porous graphene oxide/hydrogel nanocomposites and their ability for efficient adsorption of methylene blue. RSC Adv. 2016;6(13):10430–7.

    Article  ADS  CAS  Google Scholar 

  8. Wang J, et al. Self-assembled peptide nanofibers on graphene oxide as a novel nanohybrid for biomimetic mineralization of hydroxyapatite. Carbon. 2015;89:20–30.

    Article  CAS  Google Scholar 

  9. Kundu N, et al. Graphene oxide and pluronic copolymer aggregates–possible route to modulate the adsorption of fluorophores and imaging of live cells. J Phys Chem C. 2015;119(44):25023–35.

    Article  CAS  Google Scholar 

  10. Zhou T, Zhou X, Xing D. Controlled release of doxorubicin from graphene oxide based charge-reversal nanocarrier. Biomaterials. 2014;35(13):4185–94.

    Article  CAS  PubMed  Google Scholar 

  11. Oliveira AM, et al. Graphene oxide thin films with drug delivery function. Nanomaterials. 2022;12(7):1149.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Pandey N, Bohra BS, Tiwari H, Pal M, Negi PB, Dandpat A, Mehta S, N. G. Sahoo NG. Development of biodegradable chitosan/graphene oxide nanocomposite via spray drying method for drug loading and delivery application. J Drug Deliv Sci Technol. 2022;103555.

  13. Rasoulzadehzali M, Namazi H. Facile preparation of antibacterial chitosan/graphene oxide-Ag bio-nanocomposite hydrogel beads for controlled release of doxorubicin. Int J Biol Macromol. 2018;116:54–63.

    Article  CAS  PubMed  Google Scholar 

  14. Dehnad D, Jafari SM, Afrasiabi M. Influence of drying on functional properties of food biopolymers: from traditional to novel dehydration techniques. Trends Food Sci Technol. 2016;57:116–31.

    Article  CAS  Google Scholar 

  15. Rehman S, et al. Fabrication, evaluation, in vivo pharmacokinetic and toxicological analysis of pH-sensitive eudragit S-100-coated hydrogel beads: a promising strategy for colon targeting. AAPS PharmSciTech. 2021;22(6):1–17.

    Article  Google Scholar 

  16. Li Q, et al. Recent trends in the development of hydrogel therapeutics for the treatment of central nervous system disorders. NPG Asia Mater. 2022;14(1):1–14.

    Article  ADS  MathSciNet  Google Scholar 

  17. Kusuma K, Nischala M, Swathi B, Ramkanth S, Kusuma S. Formulation and evaluation of Losartan hydrogel beads. Int J Pharm Drug Anal. 2014;2:788–95.

    Google Scholar 

  18. Gombotz WR, Wee SF. Protein release from alginate matrices. Adv Drug Deliv Rev. 2012;64:194–205.

    Article  Google Scholar 

  19. Nochos A, Douroumis D, Bouropoulos N. In vitro release of bovine serum albumin from alginate/HPMC hydrogel beads. Carbohyd Polym. 2008;74(3):451–7.

    Article  CAS  Google Scholar 

  20. Pervez S, et al. Agarose hydrogel beads: an effective approach to improve the catalytic activity, stability and reusability of fungal amyloglucosidase of GH15 family. Catal Lett. 2018;148(9):2643–53.

    Article  CAS  Google Scholar 

  21. Jadach B, Świetlik W, Froelich A. Sodium alginate as a pharmaceutical excipient: novel applications of a well-known polymer. J Pharm Sci. 2022.

  22. Bajpai S, Sharma S. Investigation of swelling/degradation behaviour of alginate beads crosslinked with Ca 2+ and Ba 2+ ions. React Funct Polym. 2004;59(2):129–40.

    Article  CAS  Google Scholar 

  23. Chan E-S, et al. Prediction models for shape and size of ca-alginate macrobeads produced through extrusion–dripping method. J Colloid Interface Sci. 2009;338(1):63–72.

    Article  ADS  CAS  PubMed  Google Scholar 

  24. Buss A, Locs J. Effects of calcium and alginate concentration on the calcium-deficient hydroxyapatite hydrogel bead formation. Key Engineering Materials. Trans Tech Publ. 2017. 

  25. Cypes SH, Saltzman WM, Giannelis EP. Organosilicate-polymer drug delivery systems: controlled release and enhanced mechanical properties. J Control Release. 2003;90(2):163–9.

    Article  CAS  PubMed  Google Scholar 

  26. Justin R, Chen B. Characterisation and drug release performance of biodegradable chitosan–graphene oxide nanocomposites. Carbohyd Polym. 2014;103:70–80.

    Article  CAS  Google Scholar 

  27. Jebel FS, Almasi H. Morphological, physical, antimicrobial and release properties of ZnO nanoparticles-loaded bacterial cellulose films. Carbohyd Polym. 2016;149:8–19.

    Article  Google Scholar 

  28. Rasoulzadeh M, Namazi H. Carboxymethyl cellulose/graphene oxide bio-nanocomposite hydrogel beads as anticancer drug carrier agent. Carbohyd Polym. 2017;168:320–6.

    Article  CAS  Google Scholar 

  29. Song E, et al. Hyaluronic acid-decorated graphene oxide nanohybrids as nanocarriers for targeted and pH-responsive anticancer drug delivery. ACS Appl Mater Interfaces. 2014;6(15):11882–90.

    Article  CAS  PubMed  Google Scholar 

  30. Wang H, et al. Chlorotoxin-conjugated graphene oxide for targeted delivery of an anticancer drug. Int J Nanomed. 2014;9:1433.

    Google Scholar 

  31. Barkhordari S, Yadollahi M, Namazi H. pH sensitive nanocomposite hydrogel beads based on carboxymethyl cellulose/layered double hydroxide as drug delivery systems. J Polym Res. 2014;21(6):1–9.

    Article  CAS  Google Scholar 

  32. Kulkarni RV, et al. pH-responsive interpenetrating network hydrogel beads of poly (acrylamide)-g-carrageenan and sodium alginate for intestinal targeted drug delivery: Synthesis, in vitro and in vivo evaluation. J Colloid Interface Sci. 2012;367(1):509–17.

    Article  ADS  CAS  PubMed  Google Scholar 

  33. Aquino RP, et al. Piroxicam loaded alginate beads obtained by prilling/microwave tandem technique: morphology and drug release. Carbohyd Polym. 2012;89(3):740–8.

    Article  CAS  Google Scholar 

  34. Zhuang Y, et al. Alginate/graphene double-network nanocomposite hydrogel beads with low-swelling, enhanced mechanical properties, and enhanced adsorption capacity. J Mater Chem A. 2016;4(28):10885–92.

    Article  CAS  Google Scholar 

  35. Shin J, et al. Larvicidal composite alginate hydrogel combined with a Pickering emulsion of essential oil. Carbohyd Polym. 2021;254:117381.

    Article  CAS  Google Scholar 

  36. Wang J, et al. Controlled release of anticancer drug using graphene oxide as a drug-binding effector in konjac glucomannan/sodium alginate hydrogels. Colloids Surf B. 2014;113:223–9.

    Article  CAS  Google Scholar 

  37. Korsmeyer RW, et al. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm. 1983;15(1):25–35.

    Article  CAS  Google Scholar 

  38. Li S, et al. A common profile for polymer-based controlled releases and its logical interpretation to general release process. J Pharm Pharm Sci. 2006;9(2):238–44.

    CAS  PubMed  Google Scholar 

  39. Higuchi T. Mechanism of sustained‐action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci. 1963;52(12):1145–9.

  40. Zhang J, et al. Safe and effective removal of urea by urease-immobilized, carboxyl-functionalized PES beads with good reusability and storage stability. ACS Omega. 2019;4(2):2853–62.

    Article  CAS  Google Scholar 

  41. Zhang B, et al. Heparin modified graphene oxide for pH-sensitive sustained release of doxorubicin hydrochloride. Mater Sci Eng C. 2017;75:198–206.

    Article  CAS  Google Scholar 

  42. Gurunathan S, et al. Oxidative stress-mediated antibacterial activity of graphene oxide and reduced graphene oxide in Pseudomonas aeruginosa. Int J Nanomed. 2012;7:5901.

    Article  CAS  Google Scholar 

  43. Tsao CT, et al. Antibacterial activity and biocompatibility of a chitosan–γ-poly (glutamic acid) polyelectrolyte complex hydrogel. Carbohyd Res. 2010;345(12):1774–80.

    Article  CAS  Google Scholar 

  44. Gadkari RR, et al. Green synthesis of chitosan-cinnamaldehyde cross-linked nanoparticles: characterization and antibacterial activity. Carbohyd Polym. 2019;226:115298.

    Article  CAS  Google Scholar 

  45. Sandle T. Antibiotics and preservatives. Pharmaceutical Microbiology: Essentials for Quality Assurance and Quality Control. 2016;171–83.

  46. Liao K-H, et al. Cytotoxicity of graphene oxide and graphene in human erythrocytes and skin fibroblasts. ACS Appl Mater Interfaces. 2011;3(7):2607–15.

    Article  CAS  PubMed  Google Scholar 

  47. Khan SA, Akhtar MJ. Structural modification and strategies for the enhanced doxorubicin drug delivery. Bioorg Chem. 2022:105599.

  48. Pond GR, et al. The prognostic importance of metastatic site in men with metastatic castration-resistant prostate cancer. Eur Urol. 2014;65(1):3–6.

    Article  PubMed  Google Scholar 

  49. McCarty MF, Whitaker J. Manipulating tumor acidification as a cancer treatment strategy. Altern Med Rev. 2010;15(3):264–72.

    PubMed  Google Scholar 

  50. Bao C, et al. Graphene oxide beads for fast clean-up of hazardous chemicals. J Mater Chem A. 2016;4(24):9437–46.

    Article  CAS  Google Scholar 

  51. Rehman S, et al. Enteric-coated Ca-alginate hydrogel beads: a promising tool for colon targeted drug delivery system. Polym Bull. 2021;78(9):5103–17.

    Article  CAS  Google Scholar 

  52. Banoon SR, Ghasemian A. The characters of graphene oxide nanoparticles and doxorubicin against HCT-116 colorectal cancer cells in vitro. J Gastrointest Cancer. 2021:1–5.

  53. Bhawal P, et al. Synthesis and characterization of graphene oxide filled ethylene methyl acrylate hybrid nanocomposites. RSC Adv. 2016;6(25):20781–90.

    Article  ADS  CAS  Google Scholar 

  54. Shahriary L, Athawale AA. Graphene oxide synthesized by using modified hummers approach. Int J Renew Energy Environ Eng. 2014;2(01):58–63.

    Google Scholar 

  55. Deb A, Vimala R. Natural and synthetic polymer for graphene oxide mediated anticancer drug delivery—a comparative study. Int J Biol Macromol. 2018;107:2320–33.

    Article  CAS  PubMed  Google Scholar 

  56. Marcano DC, et al. Improved synthesis of graphene oxide. ACS Nano. 2010;4(8):4806–14.

    Article  CAS  PubMed  Google Scholar 

  57. Rao KM, Rao K, Sudhakar P, Rao KC, Subha M. Synthesis and characterization of biodegradable Poly (Vinyl caprolactam) grafted on to sodium alginate and its microgels for controlled release studies of an anticancer drug. 2013.

  58. Tubón Usca G, et al. Preparation of graphene oxide as biomaterials for drug adsorption. in AIP Conference Proceedings. 2015. American Institute of Physics.

  59. Gholamian S, Nourani M, Bakhshi N. Formation and characterization of calcium alginate hydrogel beads filled with cumin seeds essential oil. Food Chem. 2021;338:128143.

    Article  CAS  PubMed  Google Scholar 

  60. de Araújo TP, et al. Acetaminophen removal by calcium alginate/activated hydrochar composite beads: batch and fixed-bed studies. Int J Biol Macromol. 2022;203:553–62.

    Article  PubMed  Google Scholar 

  61. Sengupta I, et al. In-vitro release study through novel graphene oxide aided alginate based pH-sensitive drug carrier for gastrointestinal tract. Mater Today Commun. 2021;26:101737.

    Article  CAS  Google Scholar 

  62. Ren L, et al. A smart pH responsive graphene/polyacrylamide complex via noncovalent interaction. Nanotechnology. 2010;21(33):335701.

    Article  PubMed  Google Scholar 

  63. He Y, et al. Alginate/graphene oxide fibers with enhanced mechanical strength prepared by wet spinning. Carbohyd Polym. 2012;88(3):1100–8.

    Article  CAS  Google Scholar 

  64. Fan J, et al. Mechanically strong graphene oxide/sodium alginate/polyacrylamide nanocomposite hydrogel with improved dye adsorption capacity. J Mater Chem A. 2013;1(25):7433–43.

    Article  CAS  Google Scholar 

  65. Naghshineh N, Tahvildari K, Nozari M. Preparation of chitosan, sodium alginate, gelatin and collagen biodegradable sponge composites and their application in wound healing and curcumin delivery. J Polym Environ. 2019;27(12):2819–30.

    Article  CAS  Google Scholar 

  66. Segi N, Yotsuyanagi T, Ikeda K. Interaction of calcium-induced alginate gel beads with propranolol. Chem Pharm Bullet. 1989;37(11):3092–5.

    Article  CAS  Google Scholar 

  67. Yotsuyanagi T, et al. Acid-induced and calcium-induced gelation of alginic acid: bead formation and pH-dependent swelling. Chem Pharm Bull. 1991;39(4):1072–4.

    Article  CAS  Google Scholar 

  68. Yotsuyanagi T, et al. Effects of monovalent metal ions and propranolol on the calcium association in calcium-induced alginate gel beads. Chem Pharm Bullet. 1990;38(11):3124–6.

  69. Zhang J, Wang Q, Wang A. In situ generation of sodium alginate/hydroxyapatite nanocomposite beads as drug-controlled release matrices. Acta Biomater. 2010;6(2):445–54.

    Article  CAS  PubMed  Google Scholar 

  70. Dainty A, et al. Stability of alginate-immobilized algal cells. Biotechnol Bioeng. 1986;28(2):210–6.

    Article  CAS  PubMed  Google Scholar 

  71. Elnashar MM, et al. Surprising performance of alginate beads for the release of low-molecular-weight drugs. J Appl Polym Sci. 2010;116(5):3021–6.

    Article  CAS  Google Scholar 

  72. Sudhakar K, Moloi SJ, Rao KM. Graphene oxide/poly (N-isopropyl acrylamide)/sodium alginate-based dual responsive composite beads for controlled release characteristics of chemotherapeutic agent. Iran Polym J. 2017;26(7):521–30.

    Article  CAS  Google Scholar 

  73. Zare-Akbari Z, et al. PH-sensitive bionanocomposite hydrogel beads based on carboxymethyl cellulose/ZnO nanoparticle as drug carrier. Int J Biol Macromol. 2016;93:1317–27.

    Article  CAS  PubMed  Google Scholar 

  74. Xie M, et al. Non-covalent modification of graphene oxide nanocomposites with chitosan/dextran and its application in drug delivery. RSC Adv. 2016;6(11):9328–37.

    Article  ADS  CAS  Google Scholar 

  75. Hao G, Xu ZP, Li L. Manipulating extracellular tumour pH: an effective target for cancer therapy. RSC Adv. 2018;8(39):22182–92.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  76. Henkelman S, et al. Standardization of incubation conditions for hemolysis testing of biomaterials. Mater Sci Eng C. 2009;29(5):1650–4.

    Article  CAS  Google Scholar 

  77. Jin X, et al. High strength graphene oxide/chitosan composite screws with a steel-concrete structure. Carbohyd Polym. 2019;214:167–73.

    Article  CAS  Google Scholar 

  78. Liu S, et al. Antibacterial activity of graphite, graphite oxide, graphene oxide, and reduced graphene oxide: membrane and oxidative stress. ACS Nano. 2011;5(9):6971–80.

    Article  CAS  PubMed  Google Scholar 

  79. Krishnamoorthy K, et al. Antibacterial activity of graphene oxide nanosheets. Sci Adv Mater. 2012;4(11):1111–7.

    Article  CAS  Google Scholar 

  80. Majidi HJ, et al. Investigating the best strategy to diminish the toxicity and enhance the antibacterial activity of graphene oxide by chitosan addition. Carbohyd Polym. 2019;225:115220.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan

    Sadia Rehman, Asadullah Madni, Qazi Adnan Jameel, Hina Shoukat & Afifa Shafiq

  2. Department of Pharmaceutics, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan

    Faisal Usman

  3. Department of Mechanical Engineering, COMSATS University Islamabad, Sahiwal Campus, Sahiwal, Pakistan

    M. Rafi Raza

  4. Department of Mechanical Engineering, Universiti Teknologi PETRONAS, Seri Iskandar, Perak, Malaysia

    Faiz Ahmad

  5. Quaid-E-Azam College of Pharmacy, Sahiwal, 57000, Pakistan

    Hina Shoukat

  6. Department of Microbiology and Molecular Genetics, Bahauddin Zakariya University, Multan, Pakistan

    Hamdan Aali

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  1. Sadia Rehman
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  2. Asadullah Madni
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  3. Qazi Adnan Jameel
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Contributions

Sadia Rehman: Ph.D scholar, develop the methodology and perform the experimentation and analysis. She is also the core writer of this manuscript. Asadullah Madni: supervisor, conceptualisation, and review. Qazi Adnan Jameel: co-supervisor, resource, and review. Faisal Usman: review. M. Rafi Raza: experimentation, analysis, and editing/review. Faiz Ahmad: co-supervisor and characterization. Hina Shoukat: analysis and review. Hamdan Aali: experimetation. Afifa Shafiq: review.

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Correspondence to Asadullah Madni.

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Rehman, S., Madni, A., Jameel, Q.A. et al. RETRACTED ARTICLE: Natural Polymer-Based Graphene Oxide Bio-nanocomposite Hydrogel Beads: Superstructures with Advanced Potentials for Drug Delivery. AAPS PharmSciTech 23, 304 (2022). https://doi.org/10.1208/s12249-022-02456-w

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