Generic placeholder image

Current Drug Delivery


ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Oxidative Coupling Assembly Induced Bio-engineered Quercetin Microspheres for the Gastrosparing Delivery of Diclofenac Sodium

Author(s): Vishal Sharma, Girdhari Lal Gupta and Manu Sharma*

Volume 21, Issue 4, 2024

Published on: 27 March, 2023

Page: [582 - 591] Pages: 10

DOI: 10.2174/1567201820666230308100040

Price: $65


Objective: The study aimed to develop microspheres of quercetin by oxidative coupling assembly and these microspheres were used to deliver diclofenac sodium without causing gastrotoxicity.

Methods: The oxidative coupling assembly of quercetin was carried out in the presence of copper sulfate to yield quercetin microspheres. The microsphere of quercetin was loaded with diclofenac sodium (QP-Diclo). The carrageenan induced paw edema in rats was used for anti-inflammatory action was studied by using and acetic acid-induced writhing in mice was used to study the analgesic potential of the QP loaded microspheres. The ulcerogenecity and gastrotoxicity comparison was made between diclofenac and QP-Diclo.

Results: The oxidative coupling assembly of quercetin resulted in microspheres of 10-20 μm in size, which were loaded with diclofenac sodium (QP-Diclo). The marked anti-inflammatory activity was observed by QP-Diclo treatment using carrageenan induced paw edema (in rats) and better analgesic activity than diclofenac sodium in mice. The administration of QP-Diclo significantly elevated the diminished overall nitrite/nitrate extent and thiobarbituric acid reactive and significantly increased the diminished superoxide dismutase activity in comparison to diclofenac sodium in gastric mucosa.

Conclusion: The results suggested that dietary polyphenol quercetin can be converted to microspheres by oxidative coupling assembly and can be used to deliver diclofenac sodium without causing gastrotoxicity.

Keywords: Quercetin, diclofenac sodium, microspheres, gastrotoxicity, polyphenols, flavonoids.

Graphical Abstract
Patra, J.K.; Das, G.; Fraceto, L.F.; Campos, E.V.R.; Rodriguez-Torres, M.P.; Acosta-Torres, L.S.; Diaz-Torres, L.A.; Grillo, R.; Swamy, M.K.; Sharma, S.; Habtemariam, S.; Shin, H.S. Nano based drug delivery systems: recent developments and future prospects. J. Nanobiotechnology, 2018, 16(1), 71.
[] [PMID: 30231877]
Mohammadian, M.; Waly, M.I.; Moghadam, M.; Emam-Djomeh, Z.; Salami, M.; Moosavi-Movahedi, A.A. Nanostructured food proteins as efficient systems for the encapsulation of bioactive compounds. Food Sci. Hum. Wellness, 2020, 9(3), 199-213.
Omer, A.M.; Ahmed, M.S.; El-Subruiti, G.M.; Khalifa, R.E.; Eltaweil, A.S. pH-sensitive alginate/carboxymethyl chitosan/aminated chitosan microcapsules for efficient encapsulation and delivery of diclofenac sodium. Pharmaceutics, 2021, 13(3), 338.
[] [PMID: 33807967]
Gopinath, V.; Saravanan, S.; Al-Maleki, A.R.; Ramesh, M.; Vadivelu, J. A review of natural polysaccharides for drug delivery applications: Special focus on cellulose, starch and glycogen. Biomed. Pharmacother., 2018, 107, 96-108.
[] [PMID: 30086465]
Lee, H.A.; Ma, Y.; Zhou, F.; Hong, S.; Lee, H. Material-independent surface chemistry beyond polydopamine coating. Acc. Chem. Res., 2019, 52(3), 704-713.
[] [PMID: 30835432]
Quideau, S.; Deffieux, D.; Douat-Casassus, C.; Pouységu, L. Plant polyphenols: chemical properties, biological activities, and synthesis. Angew. Chem. Int. Ed., 2011, 50(3), 586-621.
[] [PMID: 21226137]
Ye, Q.; Zhou, F.; Liu, W. Bioinspired catecholic chemistry for surface modification. Chem. Soc. Rev., 2011, 40(7), 4244-4258.
[] [PMID: 21603689]
Sunoqrot, S.; Al-Debsi, T.; Al-Shalabi, E.; Hasan Ibrahim, L.; Faruqu, F.N.; Walters, A.; Palgrave, R.; Al-Jamal, K.T. Bioinspired polymeriza-tion of quercetin to produce a curcumin-loaded nanomedicine with potent cytotoxicity and cancer targeting potential in vivo. ACS Biomater. Sci. Eng., 2019, 5(11), 6036-6045.
[] [PMID: 33405725]
Kudaer, N.B.; Risan, M.H.; Yousif, E.; Kadhom, M.; Raheem, R.; Salman, I. Effect of zinc oxide nanoparticles on capsular gene expression in Klebsiella pneumoniae isolated from clinical samples. Biomimetics (Basel), 2022, 7(4), 180.
[] [PMID: 36412708]
Batiha, G.E.S.; Beshbishy, A.M.; Ikram, M.; Mulla, Z.S.; El-Hack, M.E.A.; Taha, A.E.; Algammal, A.M.; Elewa, Y.H.A. The pharmacological activity, biochemical properties, and pharmacokinetics of the major natural polyphenolic flavonoid: Quercetin. Foods, 2020, 9(3), 374.
[] [PMID: 32210182]
Parhi, B.; Bharatiya, D.; Swain, S.K. Application of quercetin flavonoid based hybrid nanocomposites: A review. Saudi Pharm. J., 2020, 28(12), 1719-1732.
[] [PMID: 33424263]
Sunoqrot, S.; Al-Shalabi, E.; Messersmith, P.B. Facile synthesis and surface modification of bioinspired nanoparticles from quercetin for drug delivery. Biomater. Sci., 2018, 6(10), 2656-2666.
[] [PMID: 30140818]
Mittal, A.K.; Kumar, S.; Banerjee, U.C. Quercetin and gallic acid mediated synthesis of bimetallic (silver and selenium) nanoparticles and their antitumor and antimicrobial potential. J. Colloid Interface Sci., 2014, 431, 194-199.
[] [PMID: 25000181]
Liang, H.; Li, J.; He, Y.; Xu, W.; Liu, S.; Li, Y.; Chen, Y.; Li, B. Engineering multifunctional films based on metal-phenolic networks for rational pH-responsive delivery and cell imaging. ACS Biomater. Sci. Eng., 2016, 2(3), 317-325.
[] [PMID: 33429535]
Liang, H.; Zhou, B.; Li, J.; Liu, X.; Deng, Z.; Li, B. Engineering multifunctional coatings on nanoparticles based on oxidative coupling as-sembly of polyphenols for stimuli-responsive drug delivery. J. Agric. Food Chem., 2018, 66(26), 6897-6905.
[] [PMID: 29877704]
Xu, D.; Hu, M.J.; Wang, Y.Q.; Cui, Y.L. Antioxidant activities of quercetin and its complexes for medicinal application. Molecules, 2019, 24(6), 1123.
[] [PMID: 30901869]
Musumba, C.; Pritchard, D.M.; Pirmohamed, M. Cellular and molecular mechanisms of NSAID-induced peptic ulcers. Aliment. Pharmacol. Ther., 2009, 30(6), 517-531.
[] [PMID: 19575764]
Chen, Z.; Wang, C.; Chen, J.; Li, X. Biocompatible, functional spheres based on oxidative coupling assembly of green tea polyphenols. J. Am. Chem. Soc., 2013, 135(11), 4179-4182.
[] [PMID: 23470166]
Cooper, D.L.; Harirforoosh, S. Design and optimization of PLGA-based diclofenac loaded nanoparticles. PLoS One, 2014, 9(1)e87326
[] [PMID: 24489896]
Chandiran, S.; Vyas, S.; Sharma, N.; Sharma, M. Synthesis and evaluation of antioxidant-s-(+)-Ibuprofen hybrids as gastro sparing NSAIDs. Med. Chem., 2013, 9(7), 1006-1016.
[] [PMID: 23061566]
Mohan, S.; Hobani, Y.H.; Shaheen, E.; Abou-Elhamd, A.S. abdelhaleem, A.; Alhazmi, H.A.; Abdelwahab, S.I. Girinimbine from curry leaves promotes gastro protection against ethanol induced peptic ulcers and improves healing via regulation of anti-inflammatory and antiox-idant mechanisms. Food Funct., 2020, 11(4), 3493-3505.
[] [PMID: 32248216]
Kao, L.; Liu, T.H.; Tsai, T.Y.; Pan, T.M. Beneficial effects of the commercial lactic acid bacteria product, Vigiis 101, on gastric mucosa and intestinal bacterial flora in rats. J. Microbiol. Immunol. Infect., 2020, 53(2), 266-273.
[] [PMID: 29970350]
Tang, W.; Xing, Z.; Li, C.; Wang, J.; Wang, Y. Molecular mechanisms and in vitro antioxidant effects of Lactobacillus plantarum MA2. Food Chem., 2017, 221, 1642-1649.
[] [PMID: 27979141]
Motawi, T.K.; Abd Elgawad, H.M.; Shahin, N.N. Modulation of indomethacin-induced gastric injury by spermine and taurine in rats. J. Biochem. Mol. Toxicol., 2007, 21(5), 280-288.
[] [PMID: 17912696]
Motawi, T.K.; Abd Elgawad, H.M.; Shahin, N.N. Gastroprotective effect of leptin in indomethacin-induced gastric injury. J. Biomed. Sci., 2008, 15(3), 405-412.
[] [PMID: 18181030]
Bhatia, M.; Slavin, J.; Cao, Y.; Basbaum, A.I.; Neoptolemos, J.P. Preprotachykinin-A gene deletion protects mice against acute pancreatitis and associated lung injury. Am. J. Physiol. Gastrointest. Liver Physiol., 2003, 284(5), G830-G836.
[] [PMID: 12684214]
Saijo, F.; Milsom, A.B.; Bryan, N.S.; Bauer, S.M.; Vowinkel, T.; Ivanovic, M.; Andry, C.; Granger, D.N.; Rodriguez, J.; Feelisch, M. On the dynamics of nitrite, nitrate and other biomarkers of nitric oxide production in inflammatory bowel disease. Nitric Oxide, 2010, 22(2), 155-167.
[] [PMID: 20005300]
Khattab, M.M.; Gad, M.Z.; Abdallah, D. Protective role of nitric oxide in indomethacin-induced gastric ulceration by a mechanism independ-ent of gastric acid secretion. Pharmacol. Res., 2001, 43(5), 463-467.
[] [PMID: 11394938]
Frangie, C.; Daher, J. Role of myeloperoxidase in inflammation and atherosclerosis. Review. Biomed. Rep., 2022, 16(6), 53.
[] [PMID: 35620311]
Simmons, D.L.; Botting, R.M.; Hla, T. Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol. Rev., 2004, 56(3), 387-437.
[] [PMID: 15317910]
Alotaibi, B.; Mokhtar, F.A.; El-Masry, T.A.; Elekhnawy, E.; Mostafa, S.A.; Abdelkader, D.H.; Elharty, M.E., Jnr; Saleh, A.; Negm, W.A. Antimicrobial activity of brassica rapa L. Flowers extract on gastrointestinal tract infections and antiulcer potential against Indomethacin-Induced gastric ulcer in rats supported by metabolomics profiling. J. Inflamm. Res., 2021, 14, 7411-7430.
[] [PMID: 35002276]
Tarnawski, A.S.; Ahluwalia, A.; Jones, M.K. The mechanisms of gastric mucosal injury: focus on microvascular endothelium as a key target. Curr. Med. Chem., 2012, 19(1), 4-15.
[] [PMID: 22300071]
Fornai, M.; Antonioli, L.; Colucci, R.; Pellegrini, C.; Giustarini, G.; Testai, L.; Martelli, A.; Matarangasi, A.; Natale, G.; Calderone, V.; Tuc-cori, M.; Scarpignato, C.; Blandizzi, C. NSAID-induced enteropathy: are the currently available selective COX-2 inhibitors all the same? J. Pharmacol. Exp. Ther., 2014, 348(1), 86-95.
[] [PMID: 24135073]
Li, X.; Xu, X.; Liang, T-Y.; Deng, R-M.; Chen, G. The role of nitric oxide in peptic ulcer: a narrative review. Med. Gas Res., 2021, 11(1), 42-45.
[] [PMID: 33642337]
Lanas, A. Role of nitric oxide in the gastrointestinal tract. Arthritis Res. Ther., 2008, 10(Suppl. 2), S4.
[] [PMID: 19007429]
Slomiany, B.L.; Slomiany, A. Role of endothelin-converting enzyme-1 in the suppression of constitutive nitric oxide synthase in rat gastric mucosal injury by indomethacin. Scand. J. Gastroenterol., 2000, 35(11), 1131-1136.
[] [PMID: 11145282]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy