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Current Drug Delivery

Editor-in-Chief

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

Research Article

Preparation and Optimization of Controlled Release Nanoparticles Containing Cefixime Using Central Composite Design: An Attempt to Enrich Its Antimicrobial Activity

Author(s): Mohammad Ali Mahjoub, Pedram Ebrahimnejad*, Fatemeh Shahlaee, Pouneh Ebrahimi and Zaynab Sadeghi-Ghadi

Volume 19, Issue 3, 2022

Published on: 05 January, 2022

Page: [369 - 378] Pages: 10

DOI: 10.2174/1567201818666210726160956

Price: $65

Open Access Journals Promotions 2
Abstract

Background: Due to the increased resistance against existing antibiotics, research is essential to discover new and alternative ways to control infections induced by resistant pathogens.

Objective: The goal of the current scrutinization was to enrich the dissolution rate and antibacterial property of cefixime (CEF) orally.

Methods: To achieve the desired results, chitosan nanoparticles (NPs) containing CEF were fabricated using the ionic gelation method. Central Composite design has been applied to get the optimal formulation for the delivery of CEF. The effect of three variables, such as the concentration of chitosan, tripolyphosphate, and tween 80, on the characteristics of NPs was evaluated.

Results: The optimized NPs involved a relatively monodispersed size distribution with an average diameter of 193 nm and a zeta potential of about 11 mV. The scanning tunneling microscope confirmed the size of NPs. The surface morphology of NPs was observed by scanning electron microscopy. The calorimetric analysis indicated the amorphous state of cefixime in the formulation. The dissolution rate of NPs in aqueous media was acceptable and the model of release kinetics for CEF from NPs followed the Peppas model. The potency of CEF in NPs against various types of bacteria was hopefully efficient. The ex-vivo release study demonstrated higher penetration of NPs from the rat intestine compared to free drug. The cell culture study showed the safety of the optimized formulation.

Conclusion: Chitosan NPs could be considered a significant system for the controlled delivery of CEF due to its antibacterial effectiveness.

Keywords: Nanoparticles, chitosan, cefixime, central composite, antibacterial activity, safety.

Graphical Abstract
[1]
Annunziato, G. Strategies to overcome antimicrobial resistance (AMR) making use of non-essential target inhibitors: a review. Int. J. Mol. Sci., 2019, 20(23), 5844.
[http://dx.doi.org/10.3390/ijms20235844] [PMID: 31766441]
[2]
Imran, M.; Shah, M.R.; Ullah, F.; Ullah, S.; Elhissi, A.M.; Nawaz, W.; Ahmad, F.; Sadiq, A.; Ali, I. Glycoside-based niosomal nanocarrier for enhanced in-vivo performance of Cefixime. Int. J. Pharm., 2016, 505(1-2), 122-132.
[http://dx.doi.org/10.1016/j.ijpharm.2016.03.042] [PMID: 27050867]
[3]
Maestrelli, F.; Jug, M.; Cirri, M.; Kosalec, I.; Mura, P. Characterization and microbiological evaluation of chitosan-alginate microspheres for cefixime vaginal administration. Carbohydr. Polym., 2018, 192, 176-183.
[http://dx.doi.org/10.1016/j.carbpol.2018.03.054] [PMID: 29691010]
[4]
Sindhumol, P.; Nair, C.; Harindran, J. Formulation and evaluation of floating alginate: chitosan microspheres of cefixime. Pharm. Innov. J, 2018, 7(4), 919-928.
[5]
Rangasamy, N.; Natham, N. Cefixime trihydrate loaded chitosan-alginate transdermal patches. World J. Pharm Sci, 2014, 2(9), 997-1008.
[6]
Tajmir, F.; Roosta, A. Solubility of cefixime in aqueous mixtures of deep eutectic solvents from experimental study and modeling. J. Mol. Liq., 2020, 303, 112636.
[http://dx.doi.org/10.1016/j.molliq.2020.112636]
[7]
Kamal, A.; Haghtalab, A. Experimental and thermodynamic modeling of cefixime trihydrate solubility in an aqueous deep eutectic system. J. Mol. Liq., 2020, 304, 112727.
[http://dx.doi.org/10.1016/j.molliq.2020.112727]
[8]
Telange, D.R.; Sohail, N.K.; Hemke, A.T.; Kharkar, P.S.; Pethe, A.M. Phospholipid complex-loaded self-assembled phytosomal soft nanoparticles: evidence of enhanced solubility, dissolution rate, ex vivo permeability, oral bioavailability, and antioxidant potential of mangiferin. Drug Deliv. Transl. Res., 2021, 11(3), 1056-1083.
[http://dx.doi.org/10.1007/s13346-020-00822-4] [PMID: 32696222]
[9]
Hadidi, M.; Pouramin, S.; Adinepour, F.; Haghani, S.; Jafari, S.M. Chitosan nanoparticles loaded with clove essential oil: Characterization, antioxidant and antibacterial activities. Carbohydr. Polym., 2020, 236, 116075.
[http://dx.doi.org/10.1016/j.carbpol.2020.116075] [PMID: 32172888]
[10]
Kassem, A.; Ayoub, G.M.; Malaeb, L. Antibacterial activity of chitosan nano-composites and carbon nanotubes: A review. Sci. Total Environ., 2019, 668, 566-576.
[http://dx.doi.org/10.1016/j.scitotenv.2019.02.446] [PMID: 30856567]
[11]
Alizadeh, N.; Malakzadeh, S. Antioxidant, antibacterial and anti- cancer activities of β-and γ-CDs/curcumin loaded in chitosan nanoparticles. Int. J. Biol. Macromol., 2020, 147, 778-791.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.01.206] [PMID: 31982535]
[12]
Sadeghi Ghadi, Z.; Ebrahimnejad, P. Curcumin entrapped hyaluronan containing niosomes: preparation, characterisation and in vitro/in vivo evaluation. J. Microencapsul., 2019, 36(2), 169-179.
[http://dx.doi.org/10.1080/02652048.2019.1617360] [PMID: 31104531]
[13]
Chuan, D.; Jin, T.; Fan, R.; Zhou, L.; Guo, G. Chitosan for gene delivery: Methods for improvement and applications. Adv. Colloid Interface Sci., 2019, 268, 25-38.
[http://dx.doi.org/10.1016/j.cis.2019.03.007] [PMID: 30933750]
[14]
Fernandes Patta, A.C.M.; Mathews, P.D.; Madrid, R.R.M.; Rigoni, V.L.S.; Silva, E.R.; Mertins, O. Polyionic complexes of chitosan-N-arginine with alginate as pH responsive and mucoadhesive particles for oral drug delivery applications. Int. J. Biol. Macromol., 2020, 148, 550-564.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.01.160] [PMID: 31958559]
[15]
Abul Kalam, M.; Khan, A.A.; Khan, S.; Almalik, A.; Alshamsan, A. Optimizing indomethacin-loaded chitosan nanoparticle size, encapsulation, and release using Box-Behnken experimental design. Int. J. Biol. Macromol., 2016, 87, 329-340.
[http://dx.doi.org/10.1016/j.ijbiomac.2016.02.033] [PMID: 26893052]
[16]
Qin, Y.; Li, P.; Guo, Z. Cationic chitosan derivatives as potential antifungals: A review of structural optimization and applications. Carbohydr. Polym., 2020, 236, 116002.
[http://dx.doi.org/10.1016/j.carbpol.2020.116002] [PMID: 32172836]
[17]
Asadzadeh, F.; Maleki-Kaklar, M.; Soiltanalinejad, N.; Shabani, F. Central composite design optimization of zinc removal from contaminated soil, using citric acid as biodegradable chelant. Sci. Rep., 2018, 8(1), 2633.
[http://dx.doi.org/10.1038/s41598-018-20942-9] [PMID: 29422494]
[18]
Sarrai, A.E.; Hanini, S.; Merzouk, N.K.; Tassalit, D.; Szabó, T.; Hernádi, K.; Nagy, L. Using central composite experimental design to optimize the degradation of tylosin from aqueous solution by photo-fenton reaction. Materials (Basel), 2016, 9(6), 428.
[http://dx.doi.org/10.3390/ma9060428] [PMID: 28773551]
[19]
Laid, T.M.; Abdelhamid, K.; Eddine, L.S.; Abderrhmane, B. Optimizing the biosynthesis parameters of iron oxide nanoparticles using central composite design. J. Mol. Struct., 2021, 1229, 129497.
[http://dx.doi.org/10.1016/j.molstruc.2020.129497]
[20]
Malviya, R.; Raj, S.; Fuloria, S.; Subramaniyan, V.; Sathasivam, K.; Kumari, U.; Unnikrishnan, M.D.; Porwal, O.; Hari, K.D.; Singh, A.; Chakravarthi, S.; Kumar, F.N. Evaluation of antitumor efficacy of chitosan-tamarind gum polysaccharide polyelectrolyte complex stabilized nanoparticles of simvastatin. Int. J. Nanomed., 2021, 16, 2533-2553.
[http://dx.doi.org/10.2147/IJN.S300991] [PMID: 33824590]
[21]
Ebrahimnejad, P.; Dinarvand, R.; Sajadi, A.; Jafari, M.R.; Movaghari, F.; Atyabi, F. Development and validation of an ion-pair HPLC chromatography for simultaneous determination of lactone and carboxylate forms of sn-38 in nanoparticles. Yao Wu Shi Pin Fen Xi, 2009, 17(4)
[http://dx.doi.org/10.38212/2224-6614.2602]
[22]
Yasir, M.; Chauhan, I.; Zafar, A.; Verma, M.; Noorulla, K.; Tura, A.J.; Alruwaili, N.K.; Haji, M.J.; Puri, D.; Gobena, W.G. Buspirone loaded solid lipid nanoparticles for amplification of nose to brain efficacy: Formulation development, optimization by Box-Behnken design, in-vitro characterization and in-vivo biological evaluation. J. Drug Deliv. Sci. Technol., 2021, 61, 102164.
[http://dx.doi.org/10.1016/j.jddst.2020.102164]
[23]
Taleghani, A.S.; Ebrahimnejad, P.; Heydarinasab, A.; Akbarzadeh, A. Adsorption and controlled release of iron-chelating drug from the amino-terminated PAMAM/ordered mesoporous silica hybrid materials. J. Drug Deliv. Sci. Technol., 2020, 56, 101579.
[http://dx.doi.org/10.1016/j.jddst.2020.101579]
[24]
Sadeghi-Ghadi, Z.; Vaezi, A.; Ahangarkani, F.; Ilkit, M.; Ebrahimnejad, P.; Badali, H. Potent in vitro activity of curcumin and quercetin co-encapsulated in nanovesicles without hyaluronan against Aspergillus and Candida isolates. J. Mycol. Med., 2020, 30(4), 101014.
[http://dx.doi.org/10.1016/j.mycmed.2020.101014] [PMID: 32800427]
[25]
Sharifi, F.; Nazir, I.; Asim, M.H.; Jahangiri, M.; Ebrahimnejad, P.; Matuszczak, B.; Bernkop-Schnürch, A. Zeta potential changing self-emulsifying drug delivery systems utilizing a novel Janus- headed surfactant: A promising strategy for enhanced mucus permeation. J. Mol. Liq., 2019, 291(15), 111285-111295.
[http://dx.doi.org/10.1016/j.molliq.2019.111285]
[26]
Wu, Y.; Yang, W.; Wang, C.; Hu, J.; Fu, S. Chitosan nanoparticles as a novel delivery system for ammonium glycyrrhizinate. Int. J. Pharm., 2005, 295(1-2), 235-245.
[http://dx.doi.org/10.1016/j.ijpharm.2005.01.042] [PMID: 15848008]
[27]
Gan, Q.; Wang, T.; Cochrane, C.; McCarron, P. Modulation of surface charge, particle size and morphological properties of chitosan-TPP nanoparticles intended for gene delivery. Colloids Surf. B Biointerfaces, 2005, 44(2-3), 65-73.
[http://dx.doi.org/10.1016/j.colsurfb.2005.06.001] [PMID: 16024239]
[28]
Jain, A.; Thakur, K.; Sharma, G.; Kush, P.; Jain, U.K. Fabrication, characterization and cytotoxicity studies of ionically cross-linked docetaxel loaded chitosan nanoparticles. Carbohydr. Polym., 2016, 137, 65-74.
[http://dx.doi.org/10.1016/j.carbpol.2015.10.012] [PMID: 26686106]
[29]
Dey, A.; Stenberg, J.; Dandekar, P.; Jain, R. A combinatorial study of experimental analysis and mathematical modeling: How do chitosan nanoparticles deliver therapeutics into cells? Carbohydr. Polym., 2020, 229, 115437.
[http://dx.doi.org/10.1016/j.carbpol.2019.115437] [PMID: 31826460]
[30]
Sobhani, Z.; Mohammadi, S.S.; Montaseri, H.; Khezri, E. Nanoparticles of chitosan loaded ciprofloxacin: Fabrication and antimicrobial activity. Adv. Pharm. Bull., 2017, 7(3), 427-432.
[http://dx.doi.org/10.15171/apb.2017.051] [PMID: 29071225]
[31]
Akhlaghi, S.P.; Saremi, S.; Ostad, S.N.; Dinarvand, R.; Atyabi, F. Discriminated effects of thiolated chitosan-coated pMMA paclitaxel-loaded nanoparticles on different normal and cancer cell lines. Nanomedicine, 2010, 6(5), 689-697.
[http://dx.doi.org/10.1016/j.nano.2010.01.011] [PMID: 20172052]
[32]
Mohammady, H.; Dinarvand, R.; Esfandyari, M.M.; Ebrahimnejad, P. Encapsulation of irinotecan in polymeric nanoparticles: Characterization, release kinetic and cytotoxicity evaluation. Nanomed. J., 2016, 3(3), 159-168.
[33]
Woranuch, S.; Yoksan, R. Eugenol-loaded chitosan nanoparticles: I. Thermal stability improvement of eugenol through encapsulation. Carbohydr. Polym., 2013, 96(2), 578-585.
[http://dx.doi.org/10.1016/j.carbpol.2012.08.117] [PMID: 23768603]
[34]
Keawchaoon, L.; Yoksan, R. Preparation, characterization and in vitro release study of carvacrol-loaded chitosan nanoparticles. Colloids Surf. B Biointerfaces, 2011, 84(1), 163-171.
[http://dx.doi.org/10.1016/j.colsurfb.2010.12.031] [PMID: 21296562]
[35]
Wiarachai, O.; Thongchul, N.; Kiatkamjornwong, S.; Hoven, V.P. Surface-quaternized chitosan particles as an alternative and effective organic antibacterial material. Colloids Surf. B Biointerfaces, 2012, 92, 121-129.
[http://dx.doi.org/10.1016/j.colsurfb.2011.11.034] [PMID: 22197736]
[36]
Shanmuganathan, R.; Edison, T.N.J.I.; LewisOscar, F.; Kumar, P.; Shanmugam, S.; Pugazhendhi, A. Chitosan nanopolymers: An overview of drug delivery against cancer. Int. J. Biol. Macromol., 2019, 130, 727-736.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.02.060] [PMID: 30771392]
[37]
Sharifi, F.; Jahangiri, M.; Ebrahimnejad, P. Synthesis of novel polymeric nanoparticles (methoxy-polyethylene glycol-chitosan/hyaluronic acid) containing 7-ethyl-10-hydroxycamptothecin for colon cancer therapy: in vitro, ex vivo and in vivo investigation. Artif. Cells Nanomed. Biotechnol., 2021, 49(1), 367-380.
[http://dx.doi.org/10.1080/21691401.2021.1907393] [PMID: 33851564]
[38]
Ramezani, P.; Abnous, K.; Taghdisi, S.M.; Zahiri, M.; Ramezani, M.; Alibolandi, M. Targeted MMP-2 responsive chimeric polymersomes for therapy against colorectal cancer. Colloids Surf. B Biointerfaces, 2020, 193, 111135.
[http://dx.doi.org/10.1016/j.colsurfb.2020.111135] [PMID: 32447200]
[39]
Mir, M.; Ebrahimnejad, P. Preparation and characterization of bifunctional nanoparticles of vitamin E TPGS-emulsified PLGA-PEG-FOL containing deferasirox. Nanosci. Nanotechnol. Asia, 2014, 4(2), 80-87.
[http://dx.doi.org/10.2174/2210681205666150515000224]
[40]
Binesh, N.; Farhadian, N.; Mohammadzadeh, A. Enhanced antibacterial activity of uniform and stable chitosan nanoparticles containing metronidazole against anaerobic bacterium of Bacteroides fragilis. Colloids Surf. B Biointerfaces, 2021, 202, 111691.
[http://dx.doi.org/10.1016/j.colsurfb.2021.111691] [PMID: 33743445]

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