An update on cyclodextrins as drug vehicles for antimicrobial applications

Year 2020, , 18 - 24, 01.04.2020

Ece Özcan Bülbül , Kalliopi Eleftherıadou Neslihan Üstündağ Okur , Panoraia Siafaka

https://doi.org/10.37662/jpt.2020.3

Abstract

Cyclodextrins belong to cyclic oligosaccharides comprised of α-(1,4) linked glucopyranose groups. Their interesting supramolecular cavity-like structure can host active molecules providing a breeding ground for drug delivery systems. Cyclodextrins, due to their unique functional structure, can produce host-guest complexes with active ingredients, such as drugs, peptides, proteins, etc.; the complexes resulted from intramolecular interactions leading to stable molecules vehicles. Moreover, cyclodextrins are already applied in pharmaceutical industry applications since they can induce the solubility of lipophilic compounds and provide bioavailability and excellent safety profile and stability. In this review, the basic background for cyclodextrins and their current applications in the antimicrobial field are discussed. Besides, the antibacterial and antifungal-applications in the pharmaceutical field attract most researchers because of microbes’ resistance. Regarding this, the most recent cyclodextrin inclusion complexes with antimicrobial and antifungal drugs are summarized in this article.

Keywords

Antibacterial, Antifungal, Cyclodextrins, Inclusion Complexes, Solid Dispersions

Thanks

None

References

• [1] Cid AG, Simonazzi A, Palma SD, Bermúdez JM. Solid dispersion technology as a strategy to improve the bioavailability of poorly soluble drugs. Ther Deliv. (2019); 10: 363-382. https://doi.org/10.4155/tde-2019-0007
• [2] Siafaka P, Üstündağ Okur N, Mone M, Giannakopoulou S, Er S, Pavlidou E, Karavas E, Bikiaris D. Two different approaches for oral administration of voriconazole loaded formulations: electrospun fibers versus β-cyclodextrin complexes. Int J Mol Sci. (2016) 17(3): 282. https://doi.org/10.3390/ijms17030282
• [3] Schittny A, Huwyler J, Puchkov M. Mechanisms of increased bioavailability through amorphous solid dispersions: a review. Drug Deliv. (2020); 27(1): 110-127. https://doi.org/10.1080/10717544.2019.1704940
• [4] Nabekura T, Ito Y, Cai H, Terao M, Hori R. Preparation and in vivo ocular absorption studies of disulfiram solid dispersion. Biol Pharm Bull. (2000); 23(5): 616-620. https://doi.org/10.1248/bpb.23.616
• [5] Karagianni A, Kachrimanis K, Nikolakakis I, Co-Amorphous solid dispersions for solubility and absorption improvement of drugs: composition, preparation, characterization and formulations for oral delivery. Pharmaceutics. (2018); 10(3): 98. https://doi.org/10.3390/pharmaceutics10030098
• [6] Üstündağ Okur N, Filippousi M, Okur ME, Ayla Ş, Çağlar EŞ, Yoltaş A, Siafaka PI. A novel approach for skin infections: controlled release topical mats of poly(lactic acid)/poly(ethylene succinate) blends containing Voriconazole. J Drug Deliv Sci Technol. (2018); 46: 74- 86. https://doi.org/10.1016/j.jddst.2018.05.005
• [7] Özcan Bülbül E, Mesut B, Cevher E, Öztaş E, Özsoy Y. Product transfer from lab-scale to pilot-scale of quetiapine fumarate orodispersible films using quality by design approach. J Drug Deliv Sci Technol. (2019); 54: 101358. https://doi.org/10.1016/j.jddst.2019.101358
• [8] Siafaka PI, Barmbalexis P, Bikiaris DN, Novel electrospun nanofibrous matrices prepared from poly(lactic acid)/poly(butylene adipate) blends for controlled release formulations of an anti- rheumatoid agent. Eur J Pharm Sci. (2016); 88: 12-25. https://doi.org/10.1016/j.ejps.2016.03.021
• [9] Mahmah O, Tabbakh R, Kelly A, Paradkar A. A comparative study of the effect of spray drying and hot-melt extrusion on the properties of amorphous solid dispersions containing felodipine. J Pharm Pharmacol. (2014); 66(2): 275-284. https://doi.org/10.1111/jphp.12099
• [10] Dhillon B, Goyal NK, Sharma PK. Formulation and evaluation of glibenclamide solid dispersion using different methods. Glob J Pharmacol. (2014); 8(4): 551-556. https://doi.org/10.5829/idosi.gjp.2014.8.4.84283
• [11] Pilli R, Nagabhushanam M, Kadali SDVSK. Etodolac dissolution improvement by preparation of solid dispersions. Int J Pharm Sci Res. (2014); 5(11): 4774-4791. https://doi.org/10.13040/IJPSR.0975-8232.5(11).4774-91
• [12] Szente L, Szemán J, Sohajda T. Analytical characterization of cyclodextrins: History, official methods and recommended new techniques, J Pharm Biomed Anal. (2016); 130: 347-365. https://doi.org/10.1016/j.jpba.2016.05.009
• [13] Jin ZY, Cyclodextrin chemistry, Beijing: World Scientific Publishing Company / Chemical Industry Press; (2013) 292p. ISBN:978-981-4436-79-3
• [14] Kurkov SV, Loftsson T. Cyclodextrins. Int J Pharm. (2013); 453(1): 167-180. https://doi.org/10.1016/j.ijpharm.2012.06.055
• [15] Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. J Pharm Sci. (1996); 85(10): 1017-1025. https://doi.org/10.1021/js950534b
• [16] Loftsson T, Duchene D. Cyclodextrins and their pharmaceutical applications. Int J Pharm. (2007); 329(1-2): 1-11. https://doi.org/10.1016/j.ijpharm.2006.10.044
• [17] Loftsson T, Hreinsdóttir D, Másson M. Evaluation of cyclodextrin solubilization of drugs. Int J Pharm. (2005); 302(1-2): 18-28. https://doi.org/10.1016/j.ijpharm.2005.05.042
• [18] Martin J, Díaz-Montaña EJ, Asuero AG. Cyclodextrins: past and present. In: Arora P, Dhingra N, editors. Cyclodextrin - A Versatile Ingred. Rijeka: InTech; (2018). p.3-43. https://doi.org/10.5772/intechopen.72736
• [19] Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins: basic science and product development. J Pharm Pharmacol. (2010); 62(11): 1607-1621. https://doi.org/10.1111/j.2042-7158.2010.01030.x
• [20] Jambhekar SS, Breen P. Cyclodextrins in pharmaceutical formulations II: Solubilization, binding constant, and complexation efficiency. Drug Discov Today. (2016); 21(2): 363-368. https://doi.org/10.1016/j.drudis.2015.11.016
• [21] Ogawa N, Takahashi C, Yamamoto H, Physicochemical characterization of cyclodextrin-drug interactions in the solid state and the effect of water on these interactions. J Pharm Sci. (2015); 104 (3): 942-954. https://doi.org/10.1002/jps.24319
• [22] Liu Y, Wang K, Thermodynamics of resulting complexes between cyclodextrins and bile salts. In: Morales-Rondriguez R, editor. Thermodynamics - Fundamentals and Its Application in Science. Rijeka: InTech; (2012). p. 305-318. ISBN:978-953-51-0779-8
• [23] Cirri M, Mennini N, Maestrelli F, Mura P, Ghelardini C, di Cesare Mannelli L. Development and in vivo evaluation of an innovative “hydrochlorothiazide-in cyclodextrins-in solid lipid nanoparticles” formulation with sustained release and enhanced oral bioavailability for potential hypertension treatment in pediatrics. Int J Pharm. (2017); 521(1-2): 73-83. https://doi.org/10.1016/j.ijpharm.2017.02.022
• [24] Hou X, Zhang W, He M, Lu Y, Lou K, Gao F. Preparation and characterization of β -cyclodextrin grafted N -maleoyl chitosan nanoparticles for drug delivery. Asian J Pharm Sci. (2017); 12(6): 558-568. https://doi.org/10.1016/j.ajps.2017.07.007
• [25] Sabadini E, Cosgrove T, do Carmo Egídio F. Solubility of cyclomaltooligosaccharides (cyclodextrins) in H2O and D2O: a comparative study. Carbohydr Res. (2006); 341(2): 270-274. https://doi.org/10.1016/j.carres.2005.11.004
• [26] Jansook P, Ogawa N, Loftsson T. Cyclodextrins: structure, physicochemical properties and pharmaceutical applications. Int J Pharm. (2018); 535(1-2): 272-284. https://doi.org/10.1016/j.ijpharm.2017.11.018
• [27] Jantarat C, Sirathanarun P, Ratanapongsai S, Sunyapong S, Wadu A. Curcumin-hydroxypropyl-β-cyclodextrin inclusion complex preparation methods: effect of common solvent evaporation, freeze drying, and pH shift on solubility and stability of curcumin. Trop J Pharm Res. (2014); 13(8): 1215-1223. https://doi.org/10.4314/tjpr.v13i8.4
• [28] Ghosh A, Biswas S, Ghosh T. Preparation and evaluation of silymarin β-cyclodextrin molecular inclusion complexes. J Young Pharm. (2011); 3(3): 205-210. https://doi.org/10.4103/0975-1483.83759
• [29] George SJ, Vasudevan DT. Studies on the Preparation, characterization, and solubility of 2-HP-β-cyclodextrin-meclizine HCI inclusion complexes. J Young Pharm. (2012); 4(4): 220-227. https:// doi.org/10.4103/0975-1483.104365
• [30] Loh GOK, Tan YTF, Peh KK. Enhancement of norfloxacin solubility via inclusion complexation with β-cyclodextrin and its derivative hydroxypropyl-β-cyclodextrin. Asian J Pharm Sci. (2016); 11(4): 536-546. https://doi.org/10.1016/j.ajps.2016.02.009
• [31] Sauceau M, Rodier E, Fages J. Preparation of inclusion complex of piroxicam with cyclodextrin by using supercritical carbon dioxide. J Supercrit Fluids. (2008); 47(2): 326-332. https://doi.org/10.1016/j.supflu.2008.07.006
• [32] Zhou X, Liang JF. A fluorescence spectroscopy approach for fast determination of β-cyclodextrin-guest binding constants. J Photochem Photobiol A: Chem. (2017); 349: 124-128. https://doi.org/10.1016/j.jphotochem.2017.09.032
• [33] Higuchi T, Connors KA. Phase-solubility techniques. In: Reilley CN, editor. Advances in Analytical Chemistry and Instrumentation: Volume 4. Haboken: Jonh Wiley & Sons; (1965). p. 117-212.
• [34] Zhao R, Sandström C, Zhang H, Tan T. NMR Study on the Inclusion Complexes of β-Cyclodextrin with Isoflavones. Molecules. (2016); 21 (4): 372. https://doi.org/10.3390/molecules21040372
• [35] Prestinaci F, Pezzotti P, Pantosti A. Antimicrobial resistance: a global multifaceted phenomenon. Pathog Glob Health. (2015); 109(7): 309- 318. https://doi.org/10.1179/2047773215Y.0000000030
• [36] Wiederhold N, Antifungal resistance: current trends and future strategies to combat. Infect Drug Resist. (2017); 10: 249-259. https://doi.org/10.2147/IDR.S124918
• [37] Siafaka PI, Zisi AP, Exindari MK, Karantas ID, Bikiaris DN. Porous dressings of modified chitosan with poly(2-hydroxyethyl acrylate) for topical wound delivery of levofloxacin. Carbohydr Polym. (2016); 143(5): 90-99. https://doi.org/10.1016/j.carbpol.2016.02.009
• [38] Paczkowska M, Szymanowska-Powałowska D, Mizera M, Siąkowska D, Błaszczak W, Piotrowska-Kempisty H, Cielecka-Piontek J. Cyclodextrins as multifunctional excipients: influence of inclusion into β-cyclodextrin on physicochemical and biological properties of tebipenem pivoxil. PLoS One. (2019); 14(1): e0210694. https://doi.org/10.1371/journal.pone.0210694
• [39] Jelić R, Tomović M, Stojanović S, Joksović L, Jakovljević I, Djurdjević P. Study of inclusion complex of β-cyclodextrin and levofloxacin and its effect on the solution equilibria between gadolinium(III) ion and levofloxacin. Monatshefte Für Chemie - Chem Mon. (2015); 146: 1621-1630. https://doi.org/10.1007/s00706-015-1482-z
• [40] Sanbhal N, Saitaer X, Li Y, Mao Y, Zou T, Sun G, Wang L. Controlled levofloxacin release and antibacterial properties of β- cyclodextrins-grafted polypropylene mesh devices for hernia repair. Polymers. (2018); 10(5): 493. https://doi.org/10.3390/polym10050493
• [41] Aytac Z, Yildiz ZI, Kayaci-Senirmak F, Tekinay T, Uyar T. Electrospinning of cyclodextrin/linalool-inclusion complex nanofibers: Fast-dissolving nanofibrous web with prolonged release and antibacterial activity. Food Chem. (2017); 231: 192-201. https://doi.org/10.1016/j.foodchem.2017.03.113
• [42] Szabó ZI, Deme R, Mucsi Z, Rusu A, Mare AD, Fiser B, Toma F, Sipos E, Tóth G. Equilibrium, structural and antibacterial characterization of moxifloxacin-β-cyclodextrin complex. J Mol Struct. (2018); 1166: 228-236. https://doi.org/10.1016/j.molstruc.2018.04.045
• [43] Masood F, Yasin T, Bukhari H, Mujahid M. Characterization and application of roxithromycin loaded cyclodextrin based nanoparticles for treatment of multidrug resistant bacteria. Mater Sci Eng: C. (2016); 61: 1-7. https://doi.org/10.1016/j.msec.2015.11.076
• [44] He D, Deng P, Yang L, Tan Q, Liu J, Yang M, Zhang J. Molecular encapsulation of rifampicin as an inclusion complex of hydroxypropyl -β-cyclodextrin: Design; characterization and in vitro dissolution. Colloids Surfaces B Biointerfaces. (2013); 103: 580-585. https://doi.org/10.1016/j.colsurfb.2012.10.062
• [45] Choi JM, Park K, Lee B, Jeong D, Dindulkar SD, Choi Y, Cho E, Park S, Yu J, Jung S. Solubility and bioavailability enhancement of ciprofloxacin by induced oval-shaped mono-6-deoxy-6- aminoethylamino-β-cyclodextrin. Carbohydr Polym. (2017); 163: 118-128. https://doi.org/10.1016/j.carbpol.2017.01.073
• [46] Taha M, Chai F, Blanchemain N, Neut C, Goube M, Maton M, Martel B, Hildebrand HF. Evaluation of sorption capacity of antibiotics and antibacterial properties of a cyclodextrin-polymer functionalized hydroxyapatite-coated titanium hip prosthesis. Int J Pharm. (2014); 477(1-2): 380-389. https://doi.org/10.1016/j.ijpharm.2014.10.026
• [47] Li J, Zhang S, Zhou Y, Guan S, Zhang L. Inclusion complexes of fluconazole with β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin in aqueous solution: preparation, characterization and a structural insight. J Incl Phenom Macrocycl Chem. (2016); 84: 209-217. https://doi.org/10.1007/s10847-016-0598-z
• [48] Orgován G, Kelemen H, Noszál B. Protonation and β-cyclodextrin complex formation equilibria of fluconazole. J Incl Phenom Macrocycl Chem. (2016); 84: 189-196. https://doi.org/10.1007/s10847-016-0595-2
• [49] Kim SH, Kwon JC, Park C, Han S, Yim DS, Choi JK, Cho SY, Lee HJ, Park SH, Choi SM, Choi JH, Yoo JH, Lee DG, Lee JW, Therapeutic drug monitoring and safety of intravenous voriconazole formulated with sulfobutylether β-cyclodextrin in haematological patients with renal impairment. Mycoses. (2016); 59(10): 644-651. https://doi.org/10.1111/myc.12517
• [50] Yasu T, Konuma T, Kuroda S, Takahashi S, Tojo A. Effect of cumulative intravenous voriconazole dose on renal function in hematological patients. Antimicrob Agents Chemother. (2018); 62(9): 1-4. https://doi.org/10.1128/AAC.00507-18
• [51] Sun X, Yu Z, Cai Z, Yu L, Lv Y. Voriconazole composited polyvinyl alcohol/hydroxypropyl-β-cyclodextrin nanofibers for ophthalmic delivery. PLoS One. (2016); 11(12): e0167961. https://doi.org/10.1371/journal.pone.0167961
• [52] Vass P, Démuth B, Farkas A, Hirsch E, Szabó E, Nagy B, Andersen SK, Vigh T, Verreck G, Csontos I, Marosi G, Nagy ZK. Continuous alternative to freeze drying: Manufacturing of cyclodextrin-based reconstitution powder from aqueous solution using scaled-up electrospinning. J Control Release. (2019); 298: 120-127. https://doi.org/10.1016/j.jconrel.2019.02.019
• [53] Herrera A, Rodríguez FJ, Bruna JE, Abarca RL, Galotto MJ, Guarda A, Mascayano C, Sandoval-Yáñez C, Padula M, Felipe FRS. Antifungal and physicochemical properties of inclusion complexes based on β-cyclodextrin and essential oil derivatives. Food Res Int. (2019); 121: 127-135. https://doi.org/10.1016/j.foodres.2019.03.026
• [54] Jansook P, Prajapati M, Pruksakorn P, Loftsson T. Antifungal activity of econazole nitrate/cyclodextrin complex: Effect of pH and formation of complex aggregates. Int J Pharm. (2020); 574: 118896. https://doi.org/10.1016/j.ijpharm.2019.118896
• [55] Eleamen GRA, da Costa SC, Lima-Neto RG, Neves RP, Rolim LA, Rolim-Neto PJ, Moura RO, de Aquino TM, Bento ES, Scotti MT, Mendonça-Junior FJB, Mendonça EAM, Oliveira EE. Improvement of solubility and antifungal activity of a new aminothiophene derivative by complexation with 2-hydroxypropyl-β-cyclodextrin. J Braz Chem Soc. (2016); 28(1) 116-125. https://doi.org/10.5935/0103-5053.20160153
• [56] Gontijo AV, da G Sampaio A, Koga-Ito CY, Salvador MJ. Biopharmaceutical and antifungal properties of ellagic acid- cyclodextrin using an in vitro model of invasive candidiasis. Future Microbiol. (2019); 14(11): 957-967. https://doi.org/10.2217/fmb-2019-0107
• [57] Minea B, Marangoci N, Peptanariu D, Rosca I, Nastasa V, Corciova A, Varganici C, Nicolescu A, Fifere A, Neamtu A, Mares M, Barboiu M, Pinteala M. Inclusion complexes of propiconazole nitrate with substituted β-cyclodextrins: the synthesis and in silico and in vitro assessment of their antifungal properties. New J Chem. (2016); 40(2): 1765-1776. https://doi.org/10.1039/C5NJ01811K
• [58] Teodoro GR, Gontijo AVL, Borges AC, Tanaka MH, de Morais Gouvêa Lima G, Salvador MJ, Koga-Ito CY, Gallic acid/ hydroxypropyl-β-cyclodextrin complex: Improving solubility for application on in vitro/ in vivo Candida albicans biofilms. PLoS One. (2017); 12(7) e0181199. https://doi.org/10.1371/journal.pone.0181199
• [59] Saokham P, Muankaew C, Jansook P, Loftsson T. Solubility of cyclodextrins and drug/cyclodextrin complexes. Molecules. (2018); 23(5): 1-15. https://doi.org/10.3390/molecules23051161
• [60] Jambhekar SS, Breen P. Cyclodextrins in pharmaceutical formulations I: Structure and physicochemical properties, formation of complexes, and types of complex. Drug Discov Today. (2016); 21(2): 356-362. https://doi.org/10.1016/j.drudis.2015.11.017
• [61] dos Passos Menezes P, de Araújo Andrade T, Frank LA, de Souza EPBSS, das Graças Gomes Trindade G, Trindade IAS, Serafini MR, Guterres SS, de Souza Araújo AA. Advances of nanosystems containing cyclodextrins and their applications in pharmaceuticals. Int J Pharm. (2019); 559: 312-328. https://doi.org/10.1016/j.ijpharm.2019.01.041
• [62] Tian B, Hua S, Liu J. Cyclodextrin-based delivery systems for chemotherapeutic anticancer drugs: A review. Carbohydr Polym. (2020); 232: 115805. https://doi.org/10.1016/j.carbpol.2019.115805
• [63] Shahiwala A. Cyclodextrin conjugates for colon drug delivery. J Drug Deliv Sci Technol. (2020); 55: 101448. https://doi.org/10.1016/j.jddst.2019.101448
• [64] Chaudhari P, Ghate VM, Lewis SA. Supramolecular cyclodextrin complex: Diversity, safety, and applications in o cular therapeutics. Exp Eye Res. (2019); 189: 107829. https://doi.org/10.1016/j.exer.2019.107829
• [65] Radu CD, Parteni O, Ochiuz L. Applications of cyclodextrins in medical textiles - review. J Control Release. (2016); 224: 146-157. https://doi.org/10.1016/j.jconrel.2015.12.046