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Synthesis and Characterization of Naringenin-Loaded Chitosan-Dextran Sulfate Nanocarrier

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Abstract

Purpose

The present study focused on synthesis and characterization of polymeric nanocarrier for the hydrophobic drug, naringenin (Nar), using chitosan (CS) and dextran sulfate (DS).

Method

CSDS-Nar and blank CSDS nanoparticles were prepared by complex coacervation technique. The nanoparticles were characterized by scanning electron microscopy (SEM), Fourier transform-infrared spectroscopy (FTIR), X-ray diffraction (XRD), and dynamic light scattering (DLS). Cytotoxicity evaluation of blank CSDS and CSDS-Nar was performed by MTT assay after 24-h incubation.

Result

The nanoparticles were observed to have spherical morphology. The size and zeta potential of the CSDS-Nar were ~ 337.2 ± 48.27 nm and − 34.4 ± 7.45 mV, respectively. The interactions between polymer and drug were confirmed by FTIR studies. The in vitro drug release studies showed that 80% of free naringenin was released rapidly at 36 h. On the other hand, 51% naringenin was released from CSDS-Nar at 36 h. MTT assay demonstrated that at higher dose, the cell viability of MCF-7 cells was 45% and 8% after CSDS and CSDS-Nar treatment, respectively.

Conclusion

Hence, the empirical findings of the study suggest that CSDS nanocarrier could be utilized as a promising and ideal carrier for delivery of naringenin and similar hydrophobic drugs to cancer cells.

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References

  1. De Duve C, De Barsy T, Poole B, Trouet A, Tulkens P, Van Hoof F. Lysosomotropic agents. Biochem Pharmacol. 1974;23.

  2. Shi J, Kantoff PW, Wooster R, Farokhzad OC. Cancer nanomedicine: progress, challenges and opportunities. Nat Rev Cancer. Nature Publishing Group. 2017;17:20–37.

    Article  CAS  Google Scholar 

  3. Ringsdorf H. Structure and properties of pharmacologically active polymers. J Polym Sci Symp. 1975;51:135–53.

    Article  CAS  Google Scholar 

  4. Bobo D, Robinson KJ, Islam J, Thurecht KJ, Corrie SR. Nanoparticle-based medicines: a review of FDA-approved materials and clinical trials to date. Pharm Res. Pharmaceutical Research. 2016;33:2373–87.

    CAS  PubMed  Google Scholar 

  5. Duncan R. Polymer conjugates as anticancer nanomedicines. Nat Rev Cancer. 2006;6:688–701.

    Article  CAS  Google Scholar 

  6. Fang J, Nakamura H, Maeda H. The EPR effect: unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv Drug Deliv Rev. Elsevier B.V.; 2011;63:136–51.

  7. Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R. Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol. 2007;2:751–60.

    Article  CAS  Google Scholar 

  8. Maeda H. The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Adv Enzym Regul. 2001;41:189–207.

    Article  CAS  Google Scholar 

  9. Safdar R, Omar AA, Arunagiri A, Regupathi I, Thanabalan M. Potential of chitosan and its derivatives for controlled drug release applications – a review. J Drug Deliv Sci Technol. Elsevier B.V.; 2018.

  10. Chaiyasan W, Srinivas SP, Tiyaboonchai W. Crosslinked chitosan-dextran sulfate nanoparticle for improved topical ocular drug delivery. Mol Vis. 2015;21:1224–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Bodas DS, Ige PP. Central composite rotatable design for optimization of budesonide-loaded cross-linked chitosan–dextran sulfate nanodispersion: characterization, in vitro diffusion and aerodynamic study. Drug Dev Ind Pharm. Taylor & Francis; 2019.

  12. Ibrahim SS, Osman R, Awad GAS, Mortada ND, Geneidi AS. Polysaccharides-based nanocomplexes for the prolonged delivery of enoxaparin: In-vitro and in-vivo evaluation. Int J Pharm. Elsevier B.V.; 2017;526:271–9.

  13. Chaiyasan W, Praputbut S, Kompella UB, Srinivas SP, Tiyaboonchai W. Penetration of mucoadhesive chitosan-dextran sulfate nanoparticles into the porcine cornea. Colloids Surfaces B Biointerfaces. Elsevier B.V.; 2017;149:288–96.

  14. Gera S, Talluri S, Rangaraj N, Sampathi S. Formulation and evaluation of naringenin nanosuspensions for bioavailability enhancement. AAPS PharmSciTech. AAPS PharmSciTech. 2017;18:3151–62.

    Article  CAS  Google Scholar 

  15. Salehi B, Fokou PVT, Sharifi-Rad M, Zucca P, Pezzani R, Martins N, et al. The therapeutic potential of naringenin: a review of clinical trials. Pharmaceuticals. 2019;12:1–18.

    Article  Google Scholar 

  16. Semalty A, Semalty M, Singh D, Rawat MSM. Preparation and characterization of phospholipid complexes of naringenin for effective drug delivery. J Incl Phenom Macrocycl Chem. 2010;67:253–60.

    Article  CAS  Google Scholar 

  17. Erlund I, Meririnne E, Alfthan G. Aro a. plasma kinetics and urinary excretion of the flavanones naringenin and hesperetin in humans after ingestion of orange juice and grapefruit juice. J Nutr. 2001;131:235–41.

    Article  CAS  Google Scholar 

  18. Kanaze FI, Bounartzi MI, Georgarakis M, Niopas I. Pharmacokinetics of the citrus flavanone aglycones hesperetin and naringenin after single oral administration in human subjects. Eur J Clin Nutr. 2007;61:472–7.

    Article  CAS  Google Scholar 

  19. Perrisoud D, Testa B. Inhibiting or potentiating effects of flavonoids on carbon tetrachloride-induced toxicity in isolated rat hepatocytes. Arzneimittel-Forschung/Drug Res. 1986;36:1249–53.

    Google Scholar 

  20. Kron I, Pudychová-Chovanová Z, Veliká B, Guzy J, Perjési P. (E)-2-benzylidenebenzocyclanones, part VIII: spectrophotometric determination of pK a values of some natural and synthetic chalcones and their cyclic analogues. Monatshefte fur Chemie. 2012;143:13–7.

    Article  CAS  Google Scholar 

  21. Maity S, Mukhopadhyay P, Kundu PP, Chakraborti AS. Alginate coated chitosan core-shell nanoparticles for efficient oral delivery of naringenin in diabetic animals—an in vitro and in vivo approach. Carbohydr Polym. Elsevier Ltd.; 2017;170:124–32.

  22. Sulfikkarali NK, Krishnakumar N. Evaluation of the chemopreventive response of naringenin-loaded nanoparticles in experimental oral carcinogenesis using laser-induced autofluorescence spectroscopy. Laser Phys. 2013;23.

  23. Raeisi S, Chavoshi H, Mohammadi M, Ghorbani M, Sabzichi M, Ramezani F. Naringenin-loaded nano-structured lipid carrier fortifies oxaliplatin-dependent apoptosis in HT-29 cell line. Process Biochem. Elsevier. 2019;83:168–75.

    Article  CAS  Google Scholar 

  24. Chen C, Jie X, Ou Y, Cao Y, Xu L, Wang Y, et al. Nanoliposome improves inhibitory effects of naringenin on nonalcoholic fatty liver disease in mice. Nanomedicine. 2017;12:1791–800.

    Article  CAS  Google Scholar 

  25. Ji P, Yu T, Liu Y, Jiang J, Xu J, Zhao Y, et al. Naringenin-loaded solid lipid nanoparticles: preparation, controlled delivery, cellular uptake, and pulmonary pharmacokinetics. Drug Des Devel Ther. 2016;10:911–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Khan AW, Kotta S, Ansari SH, Sharma RK, Ali J. Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid Naringenin: design, characterization, in vitro and in vivo evaluation. Drug Deliv. 2015;22:552–61.

    Article  CAS  Google Scholar 

  27. Tsai MJ, Bin HY, Fang JW, Fu YS, Wu PC. Preparation and characterization of naringenin-loaded elastic liposomes for topical application. PLoS One. 2015;10:1–12.

    Google Scholar 

  28. Shpigelman A, Shoham Y, Israeli-Lev G, Livney YD. β-Lactoglobulin-naringenin complexes: nano-vehicles for the delivery of a hydrophobic nutraceutical. Food Hydrocoll. 2014. p. 214–24.

  29. Kumar SP, Birundha K, Kaveri K, Devi KTR. Antioxidant studies of chitosan nanoparticles containing naringenin and their cytotoxicity effects in lung cancer cells. Int J Biol Macromol. Elsevier B.V.; 2015;78:87–95.

  30. Zhang P, Liu X, Hu W, Bai Y, Zhang L. Preparation and evaluation of naringenin-loaded sulfobutylether-β-cyclodextrin/chitosan nanoparticles for ocular drug delivery. Carbohydr Polym. 2016;149:224–30.

    Article  CAS  Google Scholar 

  31. George D, Maheswari PU, Begum KMMS. Cysteine conjugated chitosan based green nanohybrid hydrogel embedded with zinc oxide nanoparticles towards enhanced therapeutic potential of naringenin. React Funct Polym. Elsevier B.V; 2020;148:104480.

  32. Ahmad N, Ahmad R, Ahmad FJ, Ahmad W, Alam MA, Amir M, et al. Poloxamer-chitosan-based naringenin nanoformulation used in brain targeting for the treatment of cerebral ischemia. Saudi J Biol Sci. The Author(s); 2020;27:500–17.

  33. Agnihotri SA, Mallikarjuna NN, Aminabhavi TM. Recent advances on chitosan-based micro- and nanoparticles in drug delivery. J. Control. Release. 2004. p. 5–28.

  34. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global Cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.

    Article  Google Scholar 

  35. Anitha A, Deepagan VG, Rani VVD, Menon D, Nair S V, Jayakumar R. Preparation , characterization , in vitro drug release and biological studies of curcumin loaded dextran sulphate – chitosan nanoparticles. Carbohydr Polym. Elsevier Ltd.; 2011;84:1158–64.

  36. Ahmed TA, Aljaeid BM. Preparation, characterization, and potential application of chitosan, chitosan derivatives, and chitosan metal nanoparticles in pharmaceutical drug delivery. Drug Des Devel Ther. 2016;10:483–507.

    Article  CAS  Google Scholar 

  37. Jin YH, Hu HY, Qiao MX, Zhu J, Qi JW, Hu CJ, et al. PH-sensitive chitosan-derived nanoparticles as doxorubicin carriers for effective anti-tumor activity: preparation and in vitro evaluation. Colloids Surfaces B Biointerfaces. Elsevier B.V.; 2012;94:184–91.

  38. Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C, et al. DDSolver: an add-in program for modeling and comparison of drug dissolution profiles. AAPS J. 2010;12:263–71.

    Article  Google Scholar 

  39. Katas H, Hussain Z, Awang SA. Bovine serum albumin-loaded chitosan/dextran nanoparticles: preparation and evaluation of ex vivo colloidal stability in serum. J Nanomater. 2013;2013.

  40. Yu X, Pishko MV. Nanoparticle-based biocompatible and targeted drug delivery: characterization and in vitro studies. Biomacromolecules. 2011;12:3205–12.

    Article  CAS  Google Scholar 

  41. Bader AR, Li T, Wang W, Kohane DS, Loscalzo J, Zhang Y-Y. Preparation and characterization of SDF-1α-chitosan-dextran sulfate. J Vis Exp. 2015;95.

  42. Sharma S, Benson HAE, Mukkur TKS, Rigby P, Chen Y. Preliminary studies on the development of IgA-loaded chitosan – dextran sulphate nanoparticles as a potential nasal delivery system for protein antigens. J Microencapsul. 2013;30:283–94.

    Article  CAS  Google Scholar 

  43. Costalat M, David L, Delair T. Reversible controlled assembly of chitosan and dextran sulfate : a new method for nanoparticle elaboration. Carbohydr Polym. Elsevier Ltd.; 2014;102:717–26.

  44. Lu E, Franzblau S, Onyuksel H, Popescu C. Preparation of aminoglycoside-loaded chitosan nanoparticles using dextran sulphate as a counterion. J Microencapsul. 2009;26:346–54.

    Article  CAS  Google Scholar 

  45. Xia Y-J, Xia H, Chen L, Ying Q-S, Yu X, Li L-H, et al. Efficient delivery of recombinant human bone morphogenetic protein (rhBMP-2) with dextran sulfate-chitosan microspheres. Exp Ther Med. 2018.

  46. Chen Y, Mohanraj VJ, Parkin JE. Chitosan-dextran sulfate nanoparticles for delivery of an anti-angiogenesis peptide. Lett Pept Sci. 2003;10:621–9.

    Article  CAS  Google Scholar 

  47. Clayton KN, Salameh JW, Wereley ST, Kinzer-Ursem TL. Physical characterization of nanoparticle size and surface modification using particle scattering diffusometry. Biomicrofluidics. 2016;10:1–14.

    Article  Google Scholar 

  48. Chenthamara D, Subramaniam S, Ramakrishnan SG, Krishnaswamy S, Essa MM, Lin FH, et al. Therapeutic efficacy of nanoparticles and routes of administration. Biomater Res Biomaterials Research. 2019;23:1–29.

    Article  Google Scholar 

  49. Redhead HM, Davis SS, Illum L. Drug delivery in poly (lactide-co-glycolide) nanoparticles surface modified with poloxamer 407 and poloxamine 908: in vitro characterisation and in vivo evaluation. J Control Release. 2001;70:353–63.

    Article  CAS  Google Scholar 

  50. Singh R, Lillard JW Jr. Nanoparticle-based targeted drug delivery. Exp Mol Pathol. 2009;86:215–23.

    Article  CAS  Google Scholar 

  51. Chavan C, Bala P, Pal K, Kale SN. Cross-linked chitosan-dextran sulphate vehicle system for controlled release of ciprofloxaxin drug: an ophthalmic application. OpenNano. Elsevier Inc.; 2017;2:28–36.

  52. Perumal V, Arfuso F, Chen Y, Fox S, Dharmarajan AM. Delivery of expression constructs of secreted frizzled-related protein 4 and its domains by chitosan–dextran sulfate nanoparticles enhances their expression and anti-cancer effects. Mol Cell Biochem. Springer US; 2018;443:205–213.

  53. Müller RH. Zetapotential und Partikelladung. Kurze Theor Prakt Meûdurchfu Ehrung, Daten Interpret. Wissenschaftliche Verlagsgesellschaft: Stuttgart, Germany; 1996.

  54. Zaman P, Wang J, Blau A, Wang W, Li T, Kohane DS, et al. Incorporation of heparin-binding proteins into preformed dextran sulfate-chitosan nanoparticles. Int J Nanomedicine. 2016;11:6149–59.

    Article  CAS  Google Scholar 

  55. Gessner A, Waicz R, Lieske A, Paulke BR, Mäder K, Müller RH. Nanoparticles with decreasing surface hydrophobicities: influence on plasma protein adsorption. Int J Pharm. 2000;196:245–9.

    Article  CAS  Google Scholar 

  56. Joshi H, Hegde AR, Shetty PK, Gollavilli H, Managuli RS, Kalthur G, et al. Sunscreen creams containing naringenin nanoparticles: formulation development and in vitro and in vivo evaluations. Photodermatol Photoimmunol Photomed. 2018;34:69–81.

    Article  CAS  Google Scholar 

  57. Chaiyasan W, Srinivas SP, Tiyaboonchai W. Mucoadhesive chitosan – dextran sulfate nanoparticles. J Ocul Pharmacol Ther. 2013;29:200–7.

    Article  CAS  Google Scholar 

  58. Naskar S, Sharma S, Kuotsu K. Chitosan-based nanoparticles: an overview of biomedical applications and its preparation. J Drug Deliv Sci Technol. Elsevier B.V.; 2019;49:66–81.

  59. Magenheim B, Levy MY, Benita S. A new in vitro technique for the evaluation of drug release profile from colloidal carriers - ultrafiltration technique at low pressure. Int J Pharm. 1993;94:115–23.

    Article  CAS  Google Scholar 

  60. Freire MCLC, Alexandrino F, Marcelino HR, Picciani PHS de S, e Silva KG de H, Genre J, et al. Understanding drug release data through thermodynamic analysis. Materials (Basel) 2017;10:1–18.

  61. Rosu MC, Bratu I. Promising psyllium-based composite containing TiO2nanoparticles as aspirin-carrier matrix. Prog Nat Sci Mater Int. Elsevier; 2014;24:205–209.

  62. Siegel RA, Rathbone MJ. Fundamentals and applications of controlled release drug delivery. In: Siepmann J, Siegel RA, Rathbone MJ, editors. Fundam Appl Control Release Drug Deliv. Springer US; 2012. p. 19–43.

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Acknowledgments

The authors would like to thank Dr. Anbarasu, PMIST, for his guidance in preparation of the manuscript. The authors are also thankful for the help provided by Dr. Sai Gourang Patnaik, LAAS-CNRS, for fruitful discussion on characterization studies. The authors are also grateful to Periyar Maniammai Institute of Science & Technology for providing necessary facilities to conduct the study.

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Authors and Affiliations

  1. Department of Biotechnology, Periyar Maniammai Institute of Science & Technology, Thanjavur, India

    Shruthi Muralidharan & Kumaran Shanmugam

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  1. Shruthi Muralidharan
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  2. Kumaran Shanmugam
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Correspondence to Kumaran Shanmugam.

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Summary

The present study is a first report of using chitosan-dextran sulfate as nanocarrier for poorly water-soluble drug, naringenin (CSDS-Nar). The nanocarrier was synthesized using complex coacervation method. Characterization techniques confirmed interactions between polymer and drug. Synthesized CSDS-Nar displayed optimum size and negative surface charge. Sustained release of naringenin from CSDS-Nar was observed. CSDS-Nar reduced cell viability of MCF-7 breast cancer cells.

Teaser

The study elucidates synthesis and characterization of polymeric nanocarrier for efficient delivery of the potent yet poorly water-soluble drug, naringenin, to breast cancer cells.

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Muralidharan, S., Shanmugam, K. Synthesis and Characterization of Naringenin-Loaded Chitosan-Dextran Sulfate Nanocarrier. J Pharm Innov 16, 269–278 (2021). https://doi.org/10.1007/s12247-020-09444-2

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  • DOI: https://doi.org/10.1007/s12247-020-09444-2

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