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Green Approach Towards Synthesis and Characterization of GMO/Chitosan Nanoparticles for In Vitro Release of Quercetin: Isolated from Peels of Pomegranate Fruit

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An Author Correction to this article was published on 26 April 2021

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Abstract

In the present work, we focused on extracting, separating, formulating, and, finally, characterizing quercetin. Chitosan/GMO nanoparticles were investigated to controlled release for targeting colonic region. Quercetin is an active biomolecule isolated from peels of pomegranate fruit, separated by different chromatographic techniques, and formulated into nanoformulation to bring it to increase its aqueous solubility. Nanoparticles were prepared by using chitosan, glyceryl monooleate (GMO), and poloxamer 407 using probe sonicator and high-pressure homogenization method. Characterization of nanoparticles was carried out by particle size, zeta potential, differential scanning colorimetry (DSC), X-ray diffraction (XRD), scanning electron microscope (SEM), entrapment efficiency, loading content, in vitro release, and stability study. They showed approximately 78.82% encapsulation with an average size of 145.5 ± 0.66 nm and zeta potential + 14.7 mV. The cumulative in vitro drug release up to 24 h at 77.16% was achieved suggesting towards efficacy of green synthesized chitosan nanoparticles for colonic delivery applications. From all our findings, it can be concluded that work will facilitate the extraction, design, and fabrication of nanoparticles for the protection and sustained release of quercetin biomolecule, particularly to the colonic region. The release performance of chitosan/GMO nanoparticles loaded with quercetin at different pH conditions was greatly affected by the materials used in the preparation, which allows maximum release at colonic pH. Hence, it is a unique approach for colonic delivery of drugs having appropriate site specificity and feasibility and controlled release of biomolecule quercetin.

Graphical abstract

Biomolecule quercetin isolated from peels of pomegranate fruit, then separated and characterized by Column, Flash, GC, IR, NMR, LC-MS, HPLC and HPTLC techniques. Formulation and characterization of Qu-loaded Chi nanoparticles by FTIR, XRD, DSC, SEM, Encapsulation effiency and Loading content results influencing on critical quality attributes analysed by central composite design. Optimized Qu-loaded Chi nanoparticles had a significant sustained in-vitrorelease at colonic region.

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References

  1. Luo W, et al. Antioxidant and antiproliferative capacities of phenolics purified from Phyllanthus emblica L. fruit. Food Chem. 2011;126(1):277–282.

  2. Heim KE, Tagliaferro AR, Bobilya DJ. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J Nutr Biochem. 2002;13(10):572–84.

    Article  CAS  PubMed  Google Scholar 

  3. Erlund I. Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutr Res. 2004; 24(10): p. 851–874.

  4. Yao LH, et al. Flavonoids in food and their health benefits. Plant Foods Hum Nutr. 2004;59(3):113–22.

    Article  CAS  PubMed  Google Scholar 

  5. Liu X, et al. Identification of phenolics in the fruit of emblica (Phyllanthus emblica L.) and their antioxidant activities. Food Chem. 2008;109(4):909–915.

  6. Salgado JM, et al. Increased antioxidant content in juice enriched with dried extract of pomegranate (Punica granatum) peel. Plant Foods Hum Nutr. 2012;67(1):39–43.

    Article  CAS  Google Scholar 

  7. Lansky EP, Newman RA. Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. J Ethnopharmacol. 2007;109(2):177–206.

    Article  CAS  PubMed  Google Scholar 

  8. Qnais E, et al. Antidiarrheal activity of the aqueous extract of Punica granatum (Pomegranate) peels. Pharm Biol. 2007;45(9):715–720.

  9. Rauf A, et al. Anticancer potential of quercetin: a comprehensive review. Phytother Res. 2018;32(11):2109–30.

    Article  CAS  PubMed  Google Scholar 

  10. Negi P, Jayaprakasha G, Jena B. Antioxidant and antimutagenic activities of pomegranate peel extracts. Food Chem. 2003;80(3):393–7.

    Article  CAS  Google Scholar 

  11. Li Y, et al. Evaluation of antioxidant properties of pomegranate peel extract in comparison with pomegranate pulp extract. Food Chem. 2006;96(2):254–60.

    Article  CAS  Google Scholar 

  12. Peterson LR, Dalhoff A. Towards targeted prescribing: will the cure for antimicrobial resistance be specific, directed therapy through improved diagnostic testing? J Antimicrob Chemother. 2004;53(6):902–5.

    Article  CAS  PubMed  Google Scholar 

  13. Kawai Y, et al. Macrophage as a target of quercetin glucuronides in human atherosclerotic arteries implication in the anti-atherosclerotic mechanism of dietary flavonoids. J Biol Chem. 2008;283(14):9424–34.

    Article  CAS  PubMed  Google Scholar 

  14. Liao H, et al. A bibliometric analysis and visualization of medical big data research. Sustainability. 2018;10(1):166.

    Article  Google Scholar 

  15. Nuengchamnong N, Hermans-Lokkerbol A, Ingkaninan K. Separation and detection of the antioxidant flavonoids, rutin and quercetin, using HPLC coupled on-line with colorimetric detection of antioxidant activity. Naresuan University Journal: Science and Technology (NUJST). 2013;12(2):25–37.

    Google Scholar 

  16. Boots AW, Haenen GR, Bast A. Health effects of quercetin: from antioxidant to nutraceutical. Eur J Pharmacol. 2008;585(2–3):325–37.

    Article  CAS  PubMed  Google Scholar 

  17. Wu T-H, et al. Preparation, physicochemical characterization, and antioxidant effects of quercetin nanoparticles. Int J Pharm. 2008;346(1–2):160–8.

    Article  CAS  PubMed  Google Scholar 

  18. Patra A, et al. Formulation and evaluation of mixed polymeric micelles of quercetin for treatment of breast, ovarian, and multidrug resistant cancers. Int J Nanomed. 2018;13:2869.

    Article  CAS  Google Scholar 

  19. Ramadon D, Anwar E, Harahap Y. In vitro penetration and bioavailability of novel transdermal quercetin-loaded ethosomal gel. Indian J Pharm Sci. 2018;79(6):948–56.

    Google Scholar 

  20. Ader P, Wessmann A, Wolffram S. Bioavailability and metabolism of the flavonol quercetin in the pig. Free Radical Biol Med. 2000;28(7):1056–67.

    Article  CAS  Google Scholar 

  21. Kumari A, Yadav SK, Yadav SC. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf, B. 2010;75(1):1–18.

    Article  CAS  Google Scholar 

  22. Vijayakumar A, et al. Quercetin-loaded solid lipid nanoparticle dispersion with improved physicochemical properties and cellular uptake. AAPS Pharm Sci Tech. 2017;18(3):875–83.

    Article  CAS  Google Scholar 

  23. Sahle FF, et al. Formulation and in vitro evaluation of polymeric enteric nanoparticles as dermal carriers with pH-dependent targeting potential. Eur J Pharm Sci. 2016;92:98–109.

    Article  CAS  PubMed  Google Scholar 

  24. Kamaly N, et al. Degradable controlled-release polymers and polymeric nanoparticles: mechanisms of controlling drug release. Chem Rev. 2016;116(4):2602–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kumari A, et al. Development of biodegradable nanoparticles for delivery of quercetin. Colloids Surf, B. 2010;80(2):184–92.

    Article  CAS  Google Scholar 

  26. Han Q, et al. Quercetin nanoparticles with enhanced bioavailability as multifunctional agents toward amyloid induced neurotoxicity. J Mater Chem B. 2018;6(9):1387–93.

    Article  CAS  PubMed  Google Scholar 

  27. Khor CM, et al. Preparation and characterization of quercetin/dietary fiber nanoformulations. Carbohyd Polym. 2017;161:109–17.

    Article  CAS  Google Scholar 

  28. Dudhani AR, Kosaraju SL. Bioadhesive chitosan nanoparticles: preparation and characterization. Carbohyd Polym. 2010;81(2):243–51.

    Article  CAS  Google Scholar 

  29. Gulbake A, Jain SK. Chitosan: a potential polymer for colon-specific drug delivery system. Expert Opin Drug Deliv. 2012;9(6):713–29.

    Article  CAS  PubMed  Google Scholar 

  30. Koffi E, et al. Effect of solvent type on extraction of polyphenols from twenty three Ivorian plants. J Anim Plant Sci (JAPS). 2010;5(3):550–8.

    Google Scholar 

  31. Stalikas CD. Extraction, separation, and detection methods for phenolic acids and flavonoids. J Sep Sci. 2007;30(18):3268–95.

    Article  CAS  PubMed  Google Scholar 

  32. Chang C-C, et al. Estimation of total flavonoid content in propolis by two complementary colorimetric methods. J Food Drug Anal. 2002. 10(3).

  33. Altemimi A, et al. Simultaneous extraction, optimization, and analysis of flavonoids and polyphenols from peach and pumpkin extracts using a TLC-densitometric method. Chem Cent J. 2015;9(1):39.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Anandhakumar S, et al. Preparation of collagen peptide functionalized chitosan nanoparticles by ionic gelation method: an effective carrier system for encapsulation and release of doxorubicin for cancer drug delivery. Mater Sci Eng, C. 2017;70:378–85.

    Article  CAS  Google Scholar 

  35. Olejniczak S, Potrzebowski MJ. Solid state NMR studies and density functional theory (DFT) calculations of conformers of quercetin. Org Biomol Chem. 2004;2(16):2315–22.

    Article  CAS  PubMed  Google Scholar 

  36. Sanghavi N, Srivastava R, Malode Y. Isolation and identification of the flavonoid “quercetin” from Tridax procumbens linn. Int J Pharm Sci Res. 2014;5(4):1454.

    Google Scholar 

  37. Leela V, Saraswathy A. Quantification of pharmacologically active markers gallic acid, quercetin and lupeol from acacia leucophloea wild flowers by HPTLC method. J Anal Bioanal Tech. 2013;4:2–5.

    Google Scholar 

  38. Sarabandi K, et al. Production of reconstitutable nanoliposomes loaded with flaxseed protein hydrolysates: stability and characterization. Food Hydrocolloids. 2019;96:442–50.

    Article  CAS  Google Scholar 

  39. Pandit AA, Dash AK. Surface-modified solid lipid nanoparticulate formulation for ifosfamide: development and characterization. Nanomedicine. 2011;6(8):1397–412.

    Article  PubMed  Google Scholar 

  40. Park SN, Jo NR, Jeon SH. Chitosan-coated liposomes for enhanced skin permeation of resveratrol. J Ind Eng Chem. 2014;20(4):1481–5.

    Article  CAS  Google Scholar 

  41. Hosseini SF, et al. Two-step method for encapsulation of oregano essential oil in chitosan nanoparticles: preparation, characterization and in vitro release study. Carbohyd Polym. 2013;95(1):50–6.

    Article  CAS  Google Scholar 

  42. Shetta A, Kegere J, Mamdouh W. Comparative study of encapsulated peppermint and green tea essential oils in chitosan nanoparticles: encapsulation, thermal stability, in-vitro release, antioxidant and antibacterial activities. Int J Biol Macromol. 2019;126:731–42.

    Article  CAS  PubMed  Google Scholar 

  43. Kavaz D, Idris M, Onyebuchi C. Physiochemical characterization, antioxidative, anticancer cells proliferation and food pathogens antibacterial activity of chitosan nanoparticles loaded with Cyperus articulatus rhizome essential oils. Int J Biol Macromol. 2019;123:837–45.

    Article  CAS  PubMed  Google Scholar 

  44. Nguyen TX, et al. Chitosan-coated nano-liposomes for the oral delivery of berberine hydrochloride. J Mater Chem B. 2014;2(41):7149–59.

    Article  CAS  PubMed  Google Scholar 

  45. Mladenovska K, et al. 5-ASA loaded chitosan–Ca–alginate microparticles: preparation and physicochemical characterization. Int J Pharm. 2007;345(1–2):59–69.

    Article  CAS  PubMed  Google Scholar 

  46. Freitas C, Müller R. Correlation between long-term stability of solid lipid nanoparticles (SLN™) and crystallinity of the lipid phase. Eur J Pharm Biopharm. 1999;47(2):125–32.

    Article  CAS  PubMed  Google Scholar 

  47. Smitha B, Sridhar S, Khan A. Chitosan–sodium alginate polyion complexes as fuel cell membranes. Eur Polymer J. 2005;41(8):1859–66.

    Article  CAS  Google Scholar 

  48. Yu S-H, et al. Preparation and characterization of radical and pH-responsive chitosan–gallic acid conjugate drug carriers. Carbohyd Polym. 2011;84(2):794–802.

    Article  CAS  Google Scholar 

  49. Abdou EM, Masoud MM. Gallic acid–PAMAM and gallic acid–phospholipid conjugates, physicochemical characterization and in vivo evaluation. Pharm Dev Technol. 2018;23(1):55–66.

    Article  CAS  PubMed  Google Scholar 

  50. Venkatesan J, et al. Preparation and characterization of chitosan–carbon nanotube scaffolds for bone tissue engineering. Int J Biol Macromol. 2012;50(2):393–402.

    Article  CAS  PubMed  Google Scholar 

  51. Singh P, Verma N. Preparation and characterization of nanomicelle for ocular delivery of fluoroquinolone derivative. J Drug Deliv Ther. 2019;9(2-s):355–365.

  52. Pralhad T, Rajendrakumar K. Study of freeze-dried quercetin–cyclodextrin binary systems by DSC, FT-IR, X-ray diffraction and SEM analysis. J Pharm Biomed Anal. 2004;34(2):333–9.

    Article  CAS  PubMed  Google Scholar 

  53. Vozza G, et al. Application of Box-Behnken experimental design for the formulation and optimisation of selenomethionine-loaded chitosan nanoparticles coated with zein for oral delivery. Int J Pharm. 2018;551(1–2):257–69.

    Article  CAS  PubMed  Google Scholar 

  54. Pasparakis G, Bouropoulos N. Swelling studies and in vitro release of verapamil from calcium alginate and calcium alginate–chitosan beads. Int J Pharm. 2006;323(1–2):34–42.

    Article  CAS  PubMed  Google Scholar 

  55. Tamilvanan S, et al. Stability assessment of injectable castor oil-based nano-sized emulsion containing cationic droplets stabilized by poloxamer–chitosan emulsifier films. AAPS Pharm Sci Tech. 2010;11(2):904–9.

    Article  CAS  Google Scholar 

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Acknowledgements

The authors express their deep sense of gratitude towards Bharati Vidyapeeth College of Pharmacy (Kolhapur, Maharashtra, India) and Government College of Pharmacy (Karad, Maharashtra) for the provision of obligatory facilities to carry out present research work. The authors are profusely thankful to Dr. Riyaz Ali M. Osmani, Department of Biosciences and Bioengineering (BSBE), Indian Institute of Technology Bombay (IITB), Mumbai, for his valuable inputs and constructive suggestions.

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The original online version of this article was revised: The original version of this article unfortunately contained a mistake in figure 4. Originally, figure 4 is identical to figure 9.

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Patil, P., Killedar, S. Green Approach Towards Synthesis and Characterization of GMO/Chitosan Nanoparticles for In Vitro Release of Quercetin: Isolated from Peels of Pomegranate Fruit. J Pharm Innov 17, 764–777 (2022). https://doi.org/10.1007/s12247-021-09552-7

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