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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Research Article

Biodegradable Polymers-based Nanoparticles to Enhance the Antifungal Efficacy of Fluconazole against Candida albicans

Author(s): Noha Saleh*, Soha Elshaer and Germeen Girgis

Volume 23, Issue 5, 2022

Published on: 08 July, 2021

Page: [749 - 757] Pages: 9

DOI: 10.2174/1389201022666210708105142

Price: $65

Abstract

Background: Fluconazole (FLZ), a potent antifungal medication, is characterized by poor water solubility that reduced its antifungal efficacy.

Objective: This study aimed to prepare FLZ-loaded polymeric nanoparticles (NPs) by using different polymers and techniques as a method of enhancing the antifungal activity of FLZ.

Methods: NP1, NP2, and NP3 were prepared by the double emulsion/solvent evaporation method using PLGA, PCL, and PLA, respectively. The ionotropic pre-gelation technique was applied to prepare an alginate/chitosan-based formulation (NP4). Particle size, zeta potential, encapsulation efficiency, and loading capacity were characterized. FT-IR spectra of FLZ, the polymers, and the prepared NPs were estimated. NP4 was selected for further in-vitro release evaluation. The broth dilution method was used to assess the antifungal activity of NP4 using a resistant clinical isolate of Candida albicans.

Results: The double emulsion method produced smaller-sized particles (<390 nm) but with much lower encapsulation efficiency (<12%). Alternatively, the ionic gelation method resulted in nanosized particles with a markedly higher encapsulation efficiency of about 40%. The FT-IR spectroscopy confirmed the loading of the FLZ molecules in the polymeric network of the prepared NPs. The release profile of NP4 showed a burst initial release followed by a controlled pattern up to 24 hours with a higher percent released relative to the free FLZ suspension. NP4 was able to reduce the value of MIC of FLZ by 20 times.

Conclusion: The antifungal activity of FLZ against C. albicans was enhanced markedly via its loading in the alginate/chitosan-based polymeric matrix of NP4.

Keywords: Fluconazole, nanoparticles, fungal infection, encapsulation, particle size, polymer.

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[1]
Guinea, J. Global trends in the distribution of Candida species causing candidemia. Clin. Microbiol. Infect., 2014, 20, 5-10.
[http://dx.doi.org/10.1111/1469-0691.12539] [PMID: 24506442]
[2]
Al Aboody, M.S. Silver/silver chloride (Ag/AgCl) nanoparticles synthesized from Azadirachta indica lalex and its antibiofilm activity against fluconazole resistant Candida tropicalis. Artif. Cells Nanomed. Biotechnol., 2019, 47(1), 2107-2113.
[http://dx.doi.org/10.1080/21691401.2019.1620257] [PMID: 31137983]
[3]
Calderone, R.A.; Clancy, C.J. Candida and candidiasis; American society for microbiology press, 2011.
[http://dx.doi.org/10.1128/9781555817176]
[4]
Araujo, V.H.S.; Duarte, J.L.; Carvalho, G.C.; Silvestre, A.L.P.; Fonseca-Santos, B.; Marena, G.D.; Ribeiro, T.C.; Dos Santos Ramos, M.A.; Bauab, T.M.; Chorilli, M. Nanosystems against candidiasis: A review of studies performed over the last two decades. Crit. Rev. Microbiol., 2020, 46(5), 508-547.
[http://dx.doi.org/10.1080/1040841X.2020.1803208] [PMID: 32795108]
[5]
Muthamil, S.; Prasath, K.G.; Priya, A.; Precilla, P.; Pandian, S.K. Global proteomic analysis deciphers the mechanism of action of plant derived oleic acid against Candida albicans virulence and biofilm formation. Sci. Rep., 2020, 10(1), 5113.
[http://dx.doi.org/10.1038/s41598-020-61918-y] [PMID: 32198447]
[6]
Lo, W-H.; Deng, F-S.; Chang, C-J.; Lin, C-H. Synergistic antifungal activity of chitosan with fluconazole against candida albicans, candida tropicalis, and fluconazole-resistant strains. Molecules, 2020, 25(21), 5114.
[http://dx.doi.org/10.3390/molecules25215114] [PMID: 33153228]
[7]
Ramos-E-Silva, M.; Lima, C.M.O.; Schechtman, R.C.; Trope, B.M.; Carneiro, S. Superficial mycoses in immunodepressed patients (AIDS). Clin. Dermatol., 2010, 28(2), 217-225.
[http://dx.doi.org/10.1016/j.clindermatol.2009.12.008] [PMID: 20347666]
[8]
Fetih, G. Fluconazole-loaded niosomal gels as a topical ocular drug delivery system for corneal fungal infections. J. Drug Deliv. Sci. Technol., 2016, 35, 8-15.
[http://dx.doi.org/10.1016/j.jddst.2016.06.002]
[9]
El Rabey, H.A.; Almutairi, F.M.; Alalawy, A.I.; Al-Duais, M.A.; Sakran, M.I.; Zidan, N.S.; Tayel, A.A. Augmented control of drug-resistant Candida spp. via fluconazole loading into fungal chitosan nanoparticles. Int. J. Biol. Macromol., 2019, 141, 511-516.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.09.036] [PMID: 31499111]
[10]
Schwarz, J.C.; Kählig, H.; Matsko, N.B.; Kratzel, M.; Husa, M.; Valenta, C. Decrease of liposomal size and retarding effect on fluconazole skin permeation by lysine derivatives. J. Pharm. Sci., 2011, 100(7), 2911-2919.
[http://dx.doi.org/10.1002/jps.22513] [PMID: 21319163]
[11]
Zandi, G.; Lotfipour, F.; Ghanbarzadeh, S.; Medghalchi, M.; Hamishehkar, H. A comparative study on the potentials of nanoliposomes and nanoethosomes for fluconazole delivery. J. Drug Deliv. Sci. Technol., 2018, 44, 264-269.
[http://dx.doi.org/10.1016/j.jddst.2018.01.003]
[12]
Semnani, D.; Afrashi, M.; Alihosseini, F.; Dehghan, P.; Maherolnaghsh, M. Investigating the performance of drug delivery system of fluconazole made of nano-micro fibers coated on cotton/polyester fabric. J. Mater. Sci. Mater. Med., 2017, 28(11), 175.
[http://dx.doi.org/10.1007/s10856-017-5957-9] [PMID: 28956211]
[13]
Moazeni, M.; Kelidari, H.R.; Saeedi, M.; Morteza-Semnani, K.; Nabili, M.; Gohar, A.A.; Akbari, J.; Lotfali, E.; Nokhodchi, A. Time to overcome fluconazole resistant Candida isolates: Solid lipid nanoparticles as a novel antifungal drug delivery system. Colloids Surf. B Biointerfaces, 2016, 142, 400-407.
[http://dx.doi.org/10.1016/j.colsurfb.2016.03.013] [PMID: 26974361]
[14]
Moazeni, M.; Saeedi, M.; Kelidari, H.; Nabili, M.; Davari, A. An update on the application of nano-scaled carriers against fluconazole-resistant Candida species: Nanostructured lipid carriers or solid lipid nanoparticles? Curr Med Mycol, 2019, 5(4), 8-13.
[http://dx.doi.org/10.18502/cmm.5.4.1965] [PMID: 32104738]
[15]
Lee, C.M.; Maibach, H.I. Deep percutaneous penetration into muscles and joints. J. Pharm. Sci., 2006, 95(7), 1405-1413.
[http://dx.doi.org/10.1002/jps.20666] [PMID: 16729269]
[16]
Endo, E.H.; Makimori, R.Y.; Companhoni, M.V.P.; Ueda-Nakamura, T.; Nakamura, C.V.; Dias Filho, B.P. Ketoconazole-loaded poly-(lactic acid) nanoparticles: Characterization and improvement of antifungal efficacy in vitro against Candida and dermatophytes. J. Mycol. Med., 2020, 30(3)101003
[http://dx.doi.org/10.1016/j.mycmed.2020.101003] [PMID: 32586733]
[17]
Abedzadeh Hajar, A.; Dakhili, M.; Saghazadeh, M.; Aghaei, S.S.; Nazari, R. Synergistic antifungal effect of fluconazole combined with zno nanoparticles against candida albicans strains from vaginal candidiasis. Med. Labor. J., 2020, 14(3), 26-32.
[http://dx.doi.org/10.29252/mlj.14.3.26]
[18]
Weitz, I.S.; Maoz, M.; Panitz, D.; Eichler, S.; Segal, E. Combination of CuO nanoparticles and fluconazole: Preparation, characterization, and antifungal activity against candida albicans. J. Nanopart. Res., 2015, 17(8), 342.
[http://dx.doi.org/10.1007/s11051-015-3149-4]
[19]
Samrat, K.; Nikhil, N.S.; Karthick Raja Namasivamyam, S.; Sharath, R.; Chandraprabha, M.N.; Harish, B.G.; Muktha, H.; Kashyap, R.G. Evaluation of improved antifungal activity of fluconazole – silver nanoconjugate against pathogenic fungi. Materials today. Proceedings, 2016, 3(6), 1958-1967.
[http://dx.doi.org/10.1016/j.matpr.2016.04.097]
[20]
M. Hamad, K.; N. Mahmoud, N.; A. Al-Samad, L.; Al-Dabash, S.; Abdallah, M.; G. Al-Bakri, A. Fluconazole conjugated-gold nanorods as an antifungal nanomedicine with low cytotoxicity against human dermal fibroblasts. RSC Advances, 2020, 10(43), 25889-25897.
[http://dx.doi.org/10.1039/D0RA00297F]
[21]
Prateeksha; Singh, B. R.; Gupta, V. K.; Deeba, F.; Bajpai, R.; Pandey, V.; Naqvi, A. H.; Upreti, D. K.; Gathergood, N.; Jiang, Y. Non-toxic and ultra-small biosilver nanoclusters trigger apoptotic cell death in fluconazole-resistant candida albicans via ras signaling. Biomolecules, 2019, 9(2), 47.
[22]
Rençber, S.; Karavana, S.Y.; Yılmaz, F.F.; Eraç, B.; Nenni, M.; Özbal, S.; Pekçetin, Ç.; Gurer-Orhan, H.; Hoşgör-Limoncu, M.; Güneri, P.; Ertan, G. Development, characterization, and in vivo assessment of mucoadhesive nanoparticles containing fluconazole for the local treatment of oral candidiasis. Int. J. Nanomedicine, 2016, 11, 2641-2653.
[http://dx.doi.org/10.2147/IJN.S103762] [PMID: 27358561]
[23]
Karthikeyan, K.; Sowjanya, R.S.; Yugandhar, A.D.V.; Gopinath, S.; Korrapati, P.S. Design and development of a topical dosage form for the convenient delivery of electrospun drug loaded nanofibers. RSC Advances, 2015, 5(65), 52420-52426.
[http://dx.doi.org/10.1039/C5RA04438C]
[24]
Sharma, R.; Garg, T.; Goyal, A.K.; Rath, G. Development, optimization and evaluation of polymeric electrospun nanofiber: A tool for local delivery of fluconazole for management of vaginal candidiasis. Artif. Cells Nanomed. Biotechnol., 2016, 44(2), 524-531.
[http://dx.doi.org/10.3109/21691401.2014.966194] [PMID: 25315503]
[25]
Shah, R.R.; Magdum, C.S.; Wadkar, K.A.; Naikwade, N.S. Fluconazole topical microemulsion: Preparation and evaluation. Pharmaceuticals, 2009, 1, 2.
[26]
Soliman, O.A.E.; Mohamed, E.A.; Khatera, N.A.A. Enhanced ocular bioavailability of fluconazole from niosomal gels and microemulsions: Formulation, optimization, and in vitro-in vivo evaluation. Pharm. Dev. Technol., 2019, 24(1), 48-62.
[http://dx.doi.org/10.1080/10837450.2017.1413658] [PMID: 29210317]
[27]
Gupta, M.; Vaidya, B.; Mishra, N.; Vyas, S.P. Effect of surfactants on the characteristics of fluconazole niosomes for enhanced cutaneous delivery. Artif. Cells Blood Substit. Immobil. Biotechnol., 2011, 39(6), 376-384.
[http://dx.doi.org/10.3109/10731199.2011.611476] [PMID: 21951195]
[28]
Antonio, J.R.; Antônio, C.R.; Cardeal, I.L.S.; Ballavenuto, J.M.A.; Oliveira, J.R. Nanotechnology in dermatology. An. Bras. Dermatol., 2014, 89(1), 126-136.
[http://dx.doi.org/10.1590/abd1806-4841.20142228] [PMID: 24626657]
[29]
Zhang, L.; Pornpattananangku, D.; Hu, C-M.; Huang, C-M. Development of nanoparticles for antimicrobial drug delivery. Curr. Med. Chem., 2010, 17(6), 585-594.
[http://dx.doi.org/10.2174/092986710790416290] [PMID: 20015030]
[30]
Roque, L.; Castro, P.; Molpeceres, J.; Viana, A.S.; Roberto, A.; Reis, C.; Rijo, P.; Tho, I.; Sarmento, B.; Reis, C. Bioadhesive polymeric nanoparticles as strategy to improve the treatment of yeast infections in oral cavity: In-vitro and ex-vivo studies. Eur. Polym. J., 2018, 104, 19-31.
[http://dx.doi.org/10.1016/j.eurpolymj.2018.04.032]
[31]
Lam, S.J.; Wong, E.H.H.; Boyer, C.; Qiao, G.G. Antimicrobial polymeric nanoparticles. Prog. Polym. Sci., 2018, 76, 40-64.
[http://dx.doi.org/10.1016/j.progpolymsci.2017.07.007]
[32]
Fernandes Costa, A.; Evangelista Araujo, D.; Santos Cabral, M.; Teles Brito, I.; Borges de Menezes Leite, L.; Pereira, M.; Correa Amaral, A. Development, characterization, and in vitro-in vivo evaluation of polymeric nanoparticles containing miconazole and farnesol for treatment of vulvovaginal candidiasis. Med. Mycol., 2019, 57(1), 52-62.
[http://dx.doi.org/10.1093/mmy/myx155] [PMID: 29361177]
[33]
Lucena, P.A.; Nascimento, T.L.; Gaeti, M.P.N.; de Ávila, R.I.; Mendes, L.P.; Vieira, M.S.; Fabrini, D.; Amaral, A.C.; Lima, E.M. In vivo vaginal fungal load reduction after treatment with itraconazole-loaded polycaprolactone-nanoparticles. J. Biomed. Nanotechnol., 2018, 14(7), 1347-1358.
[http://dx.doi.org/10.1166/jbn.2018.2574] [PMID: 29944108]
[34]
Salama, A.H.; AbouSamra, M.M.; Awad, G.E.A.; Mansy, S.S. Promising bioadhesive ofloxacin-loaded polymeric nanoparticles for the treatment of ocular inflammation: Formulation and in vivo evaluation. Drug Deliv. Transl. Res., 2020, 1-15.
[http://dx.doi.org/10.1007/s13346-019-00648-9] [PMID: 33006742]
[35]
Wang, Y.; Li, P.; Kong, L. Chitosan-modified PLGA nanoparticles with versatile surface for improved drug delivery. AAPS PharmSciTech, 2013, 14(2), 585-592.
[http://dx.doi.org/10.1208/s12249-013-9943-3] [PMID: 23463262]
[36]
Kumari, A.; Yadav, S.K.; Yadav, S.C. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf. B Biointerfaces, 2010, 75(1), 1-18.
[http://dx.doi.org/10.1016/j.colsurfb.2009.09.001] [PMID: 19782542]
[37]
Gómez-Sequeda, N.; Torres, R.; Ortiz, C. Synthesis, characterization, and in vitro activity against Candida spp. of fluconazole encapsulated on cationic and conventional nanoparticles of poly(lactic-co-glycolic acid). Nanotechnol. Sci. Appl., 2017, 10, 95-104.
[http://dx.doi.org/10.2147/NSA.S96018] [PMID: 28572725]
[38]
Ramadan, E.; Borg, T.; Abdelghani, G.M.; Saleh, N.M. Transdermal microneedle-mediated delivery of polymeric lamivudine-loaded nanoparticles. J. of Pha. Tec. and Drug Res., 2016, 5(1), 1.
[http://dx.doi.org/10.7243/2050-120X-5-1]
[39]
Li, P.; Dai, Y-N.; Zhang, J-P.; Wang, A-Q.; Wei, Q. Chitosan-alginate nanoparticles as a novel drug delivery system for nifedipine. Int. J. Biomed. Sci., 2008, 4(3), 221-228.
[PMID: 23675094]
[40]
Silva, M.M.; Calado, R.; Marto, J.; Bettencourt, A.; Almeida, A.J.; Gonçalves, L.M.D. Chitosan nanoparticles as a mucoadhesive drug delivery system for ocular administration. Mar. Drugs, 2017, 15(12), 370.
[http://dx.doi.org/10.3390/md15120370] [PMID: 29194378]
[41]
Alexander, B.D. Reference method for broth dilution antifungal susceptibility testing of yeasts, 4th; Clinical and laboratory standards institute, 2017.
[42]
Unagolla, J.M.; Jayasuriya, A.C. Drug transport mechanisms and in vitro release kinetics of vancomycin encapsulated chitosan-alginate polyelectrolyte microparticles as a controlled drug delivery system. Eur. J. Pharm. Sci., 2018, 114, 199-209.
[http://dx.doi.org/10.1016/j.ejps.2017.12.012] [PMID: 29269322]
[43]
Kakkar, S.; Singh, M.; Karuppayil, S. M.; Raut, J. S.; Giansant, F.; Papucci, L.; Schiavone, N.; Nag, T. C.; Gao, N.; Yu, F.-S. X. Lipo- PEG nano-ocular formulation successfully encapsulates hydrophilic fluconazole and traverses corneal and non-corneal path to reach posterior eye segment. J. of Drug Target, 2021, ja, 1-240.
[44]
Misra, R.; Acharya, S.; Dilnawaz, F.; Sahoo, S.K. Sustained antibacterial activity of doxycycline-loaded poly(D,L-lactide-co-glycolide) and poly(ε-caprolactone) nanoparticles. Nanomedicine (Lond.), 2009, 4(5), 519-530.
[http://dx.doi.org/10.2217/nnm.09.28] [PMID: 19572818]
[45]
Scolari, I.R.; Páez, P.L.; Sánchez-Borzone, M.E.; Granero, G.E. Promising chitosan-coated alginate-tween 80 nanoparticles as rifampicin coadministered ascorbic acid delivery carrier against mycobacterium tuberculosis. AAPS PharmSciTech, 2019, 20(2), 67.
[http://dx.doi.org/10.1208/s12249-018-1278-7] [PMID: 30627867]
[46]
Wasupalli, G.K.; Verma, D. Molecular interactions in self-assembled nano-structures of chitosan-sodium alginate based polyelectrolyte complexes. Int. J. Biol. Macromol., 2018, 114, 10-17.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.03.075] [PMID: 29551510]
[47]
Verma, D.; Desai, M.S.; Kulkarni, N.; Langrana, N. Characterization of surface charge and mechanical properties of chitosan/alginate based biomaterials. Mater. Sci. Eng. C, 2011, 31(8), 1741-1747.
[http://dx.doi.org/10.1016/j.msec.2011.08.005]
[48]
Cheng, L.; Bulmer, C.; Margaritis, A. Characterization of novel composite alginate chitosan-carrageenan nanoparticles for encapsulation of BSA as a model drug delivery system. Curr. Drug Deliv., 2015, 12(3), 351-357.
[http://dx.doi.org/10.2174/1567201812666150114155948] [PMID: 26054536]
[49]
Mujtaba, A.; Hassan, K.A.M.; Imran, M. Chitosan-alginate nanoparticles as a novel drug delivery system for rutin. Inter. J. of Adv. Biotecnol. Res., 2018, 9(1), 1895-1905.
[50]
Natarajan, V.; Krithica, N.; Madhan, B.; Sehgal, P.K. Formulation and evaluation of quercetin polycaprolactone microspheres for the treatment of rheumatoid arthritis. J. Pharm. Sci., 2011, 100(1), 195-205.
[http://dx.doi.org/10.1002/jps.22266] [PMID: 20607810]
[51]
Reddy, R.S.; Kumar, L.; Pydi, C.R.; Reddy, M.S.; Verma, R. Development of fluconazole suppositories for the treatment of candida infection of genitourinary tract. Indian J. of Pharma. Edu. Res., 2018, 52(4s), s16-s22.
[http://dx.doi.org/10.5530/ijper.52.4s.71]
[52]
Sarmento, B.; Ribeiro, A.; Veiga, F.; Ferreira, D. Development and validation of a rapid reversed-phase HPLC method for the determination of insulin from nanoparticulate systems. Biomed. Chromatogr., 2006, 20(9), 898-903.
[http://dx.doi.org/10.1002/bmc.616] [PMID: 16389645]
[53]
Nagarwal, R.C.; Kumar, R.; Pandit, J.K. Chitosan coated sodium alginate-chitosan nanoparticles loaded with 5-FU for ocular delivery: In vitro characterization and In vivo study in rabbit eye. Eur. J. Pharm. Sci., 2012, 47(4), 678-685.
[http://dx.doi.org/10.1016/j.ejps.2012.08.008] [PMID: 22922098]
[54]
Panwar, R.; Pemmaraju, S.C.; Sharma, A.K.; Pruthi, V. Efficacy of ferulic acid encapsulated chitosan nanoparticles against Candida albicans biofilm. Microb. Pathog., 2016, 95, 21-31.
[http://dx.doi.org/10.1016/j.micpath.2016.02.007] [PMID: 26930164]
[55]
Han, C.; Romero, N.; Fischer, S.; Dookran, J.; Berger, A.; Doiron, A.L. Recent developments in the use of nanoparticles for treatment of biofilms. Nanotechnol. Rev., 2017, 6(5), 383-404.
[http://dx.doi.org/10.1515/ntrev-2016-0054]
[56]
Kravanja, G.; Primožič, M.; Knez, Ž.; Leitgeb, M. Chitosan-based (nano)materials for novel biomedical applications. Molecules, 2019, 24(10), 1960.
[http://dx.doi.org/10.3390/molecules24101960] [PMID: 31117310]
[57]
Goy, R.C.; de Britto, D.; Assis, O.B.G. A review of the antimicrobial activity of chitosan. Polímeros, 2009, 19(3), 241-247.
[http://dx.doi.org/10.1590/S0104-14282009000300013]
[58]
Arias, L.S.; Pessan, J.P.; Vieira, A.P.M.; Lima, T.M.T.; Delbem, A.C.B.; Monteiro, D.R. Iron oxide nanoparticles for biomedical applications: A perspective on synthesis, drugs, antimicrobial activity, and toxicity. Antibiotics (Basel), 2018, 7(2), 46.
[http://dx.doi.org/10.3390/antibiotics7020046] [PMID: 29890753]
[59]
Pemán, J.; Cantón, E.; Espinel-Ingroff, A. Antifungal drug resistance mechanisms. Expert Rev. Anti Infect. Ther., 2009, 7(4), 453-460.
[http://dx.doi.org/10.1586/eri.09.18] [PMID: 19400764]
[60]
Xia, Z-K.; Ma, Q-H.; Li, S-Y.; Zhang, D-Q.; Cong, L.; Tian, Y-L.; Yang, R-Y. The antifungal effect of silver nanoparticles on trichosporon asahii. J. Microbiol. Immunol. Infect. 2016, 49(2), 182-188.
[http://dx.doi.org/10.1016/j.jmii.2014.04.013] [PMID: 24877597]
[61]
de Lima, T.M.; Arias, L.S.; Afanaci, L.F.; Ferraresse, R.F. de S Neto, F.N.; de Lima, B.H.; Straioto, F.G.; de Camargo, E.R.; Pessan, J.P.; Monteiro, D.R. Assembly and antifungal effect of a new fluconazole-carrier nanosystem. Future Microbiol., 2020, 15(4), 273-285.
[http://dx.doi.org/10.2217/fmb-2019-0182] [PMID: 32271112]

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