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Preparation, Characterization, and Properties of Inclusion Complexes of Balofloxacin with Cyclodextrins

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Abstract

The study mainly aimed to improve the aqueous solubility of Balofloxacin (BLFX) by preparing the inclusion complexes (ICs) of BLFX with cyclodextrins (CDs). In this study, ICs in solid state were obtained by using beta-CD (β-CD), 2-hydroxypropyl-β-CD (HP-β-CD), 2, 6-dimethyl-β-CD (DM-β-CD) through a freeze-drying technique. The formation of ICs was confirmed through Fourier-transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffraction, nuclear magnetic resonance, and scanning electron microscopy. Results demonstrated that the water solubility and dissolution rates of three ICs were distinctly improved than that of parent BLFX. Bacteriostatic experiment manifested that the antibacterial effect of BLFX was not inhibited after encapsulation in CDs. The damage of BLFX to kidney and liver cells was reduced. Consequently, successful preparation of the ICs of BLFX with CDs provided possibility for devising new dosage form of BLFX, which held great promise for further applications in clinical fields.

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References

  1. Ezelarab HAA, Abbas SH, Hassan HA, Abuo-Rahma GEA. Recent updates of fluoroquinolones as antibacterial agents. Arch Pharm. 2018;351(9):e1800141. https://doi.org/10.1002/ardp.201800141.

    Article  CAS  Google Scholar 

  2. Rizvi I, Malhotra HS, Garg RK, Kumar N, Uniyal R, Pandey S. Fluoroquinolones in the management of tuberculous meningitis: systematic review and meta-analysis. J Infect. 2018;77(4):261–75. https://doi.org/10.1016/j.jinf.2018.06.009.

    Article  PubMed  Google Scholar 

  3. Alovero F. In vitro pharmacodynamic properties of a fluoroquinolone pharmaceutical derivative: hydrochloride of ciprofloxacin–aluminium complex. Int J Antimicrob Agents. 2003;21(5):446–51. https://doi.org/10.1016/s0924-8579(03)00051-7.

    Article  CAS  PubMed  Google Scholar 

  4. DLRaCM R. Aqueous solubilities of some variously substituted quinolone antimicrobials. Int J Pharm. 1990;63:237–50.

    Article  Google Scholar 

  5. Zhang ZH, Zhang Q, Zhang QQ, Chen C, He MY, Chen Q, et al. From a binary salt to salt co-crystals of antibacterial agent lomefloxacin with improved solubility and bioavailability. Acta Crystallogr Sect B: Struct Sci Cryst Eng Mater. 2015;71(Pt 4):437–46. https://doi.org/10.1107/S2052520615011191.

    Article  CAS  Google Scholar 

  6. Cheng Y, Qu H, Ma M, Xu Z, Xu P, Fang Y, et al. Polyamidoamine (PAMAM) dendrimers as biocompatible carriers of quinolone antimicrobials: an in vitro study. Eur J Med Chem. 2007;42(7):1032–8. https://doi.org/10.1016/j.ejmech.2006.12.035.

    Article  CAS  PubMed  Google Scholar 

  7. Qi Y, Zhao F, Xie X, Xu X, Ma Z. Study on the cofluorescence effect of europium (III)–yttrium (III)—Balofloxacin–sodium dodecyl sulfate system and its analytical application. Spectrosc Lett. 2014;48(5):311–6. https://doi.org/10.1080/00387010.2013.879316.

    Article  CAS  Google Scholar 

  8. Tatsuya Ito MM, Nishino T. Improved bactericidal activity of Q-35 against quinolone-resistant staphylococci. Antimicrob Agents Chemother. 1995;39:1522–5.

    Article  Google Scholar 

  9. Osamu Kozawa TU, Matsuno H, Niwa M, Nagashima S, Kanamaru M. Comparative study of pharmacokinetics of two new fluoroquinolones, Balofloxacin and Grepafloxacin, in elderly subjects. Antimicrob Agents Chemother. 1996;40:2824–8.

    Article  Google Scholar 

  10. Suzuki K, MH KI, Katoh S, Naide Y, Yanaoka M, Andoh S. Laboratory and clinical study of Balofloxacin (Q-35), a new fluoroquinolone, in urinary tract infection. Drugs. 1995;49:376–8.

    Article  CAS  Google Scholar 

  11. Shelley H, Babu RJ. Role of cyclodextrins in nanoparticle-based drug delivery systems. J Pharm Sci. 2018;107(7):1741–53. https://doi.org/10.1016/j.xphs.2018.03.021.

    Article  CAS  PubMed  Google Scholar 

  12. Tang P, Sun Q, Suo Z, Zhao L, Yang H, Xiong X, et al. Rapid and efficient removal of estrogenic pollutants from water by using beta- and gamma-cyclodextrin polymers. Chem Eng J. 2018;344:514–23. https://doi.org/10.1016/j.cej.2018.03.127.

    Article  CAS  Google Scholar 

  13. Tang P, Sun Q, Zhao L, Tang Y, Liu Y, Pu H, et al. A simple and green method to construct cyclodextrin polymer for the effective and simultaneous estrogen pollutant and metal removal. Chem Eng J. 2019;366:598–607. https://doi.org/10.1016/j.cej.2019.02.117.

    Article  CAS  Google Scholar 

  14. Yujing Guo SG, Zhai JRY, Dong S, Wang E. Cyclodextrin functionalized graphene nanosheets with high supramolecular recognition capability synthesis and host-guest inclusion for enhanced electrochemical performance. ACS Nano. 2010;4:4001–10.

    Article  Google Scholar 

  15. Lopedota A, Denora N, Laquintana V, Cutrignelli A, Lopalco A, Tricarico D, et al. Alginate-based hydrogel containing minoxidil/hydroxypropyl-beta-cyclodextrin inclusion complex for topical alopecia treatment. J Pharm Sci. 2018;107(4):1046–54. https://doi.org/10.1016/j.xphs.2017.11.016.

    Article  CAS  PubMed  Google Scholar 

  16. Le-Deygen IM, Skuredina AA, Uporov IV, Kudryashova EV. Thermodynamics and molecular insight in guest–host complexes of fluoroquinolones with β-cyclodextrin derivatives, as revealed by ATR-FTIR spectroscopy and molecular modeling experiments. Anal Bioanal Chem. 2017;409(27):6451–62. https://doi.org/10.1007/s00216-017-0590-5.

    Article  CAS  PubMed  Google Scholar 

  17. Shi Y, Peng J, Meng X, Huang T, Zhang J, He H. Turn-on fluorescent detection of captopril in urine samples based on hydrophilic hydroxypropyl beta-cyclodextrin polymer. Anal Bioanal Chem. 2018;410(28):7373–84. https://doi.org/10.1007/s00216-018-1343-9.

    Article  CAS  PubMed  Google Scholar 

  18. Kurkov SV, Loftsson T. Cyclodextrins. Int J Pharm. 2013;453(1):167–80. https://doi.org/10.1016/j.ijpharm.2012.06.055.

    Article  CAS  PubMed  Google Scholar 

  19. Charoenchaitrakool M, Dehghani F, Foster NR. Utilization of supercritical carbon dioxide for complex formation of ibuprofen and methyl-β-cyclodextrin. Int J Pharm. 2002;239:103–12.

    Article  CAS  Google Scholar 

  20. Inoue Y, Watanabe S, Suzuki R, Murata I, Kanamoto I. Evaluation of actarit/γ-cyclodextrin complex prepared by different methods. J Incl Phenom Macrocycl Chem. 2014;81(1–2):161–8. https://doi.org/10.1007/s10847-014-0445-z.

    Article  CAS  Google Scholar 

  21. Higuchi T, Connors KA. Phase solubility techniques. Adv Anal Chem Instrum 1965;4117–212.

  22. Garnero C, Chattah AK, Aloisio C, Fabietti L, Longhi M. Improving the stability and the pharmaceutical properties of Norfloxacin form C through binary complexes with beta-cyclodextrin. AAPS PharmSciTech. 2018;19(5):2255–63. https://doi.org/10.1208/s12249-018-1033-0.

    Article  CAS  PubMed  Google Scholar 

  23. Wang L, Li S, Tang P, Yan J, Xu K, Li H. Characterization and evaluation of synthetic riluzole with beta-cyclodextrin and 2,6-di-O-methyl-beta-cyclodextrin inclusion complexes. Carbohydr Polym. 2015;129:9–16. https://doi.org/10.1016/j.carbpol.2015.04.046.

    Article  CAS  PubMed  Google Scholar 

  24. He Z, Wei G, Li N, Niu M, Gong S, Wu G, et al. CCR2 and CCR5 promote diclofenac-induced hepatotoxicity in mice. Naunyn Schmiedeberg's Arch Pharmacol. 2018;392:287–97. https://doi.org/10.1007/s00210-018-1576-3.

    Article  CAS  Google Scholar 

  25. Yang R, Zhao Q, Hu DD, Xiao XR, Li F. Optimization of extraction and analytical protocol for mass spectrometry-based metabolomics analysis of hepatotoxicity. Biomed Chromatogr. 2018;32(12):e4359. https://doi.org/10.1002/bmc.4359.

    Article  CAS  PubMed  Google Scholar 

  26. Bian Z, Tian Y, Zhang Z, Xu F, Li J, Cao X. High performance liquid chromatography-electrospray ionization mass spectrometric determination of balofloxacin in human plasma and its pharmacokinetics. J Chromatogr B, Analytical technologies in the biomedical and life sciences. 2007;850(1–2):68–73. https://doi.org/10.1016/j.jchromb.2006.11.001.

    Article  CAS  Google Scholar 

  27. Wang D, Chen G, Ren L. Preparation and characterization of the sulfobutylether-beta-cyclodextrin inclusion complex of amiodarone hydrochloride with enhanced oral bioavailability in fasted state. AAPS PharmSciTech. 2017;18(5):1526–35. https://doi.org/10.1208/s12249-016-0646-4.

    Article  CAS  PubMed  Google Scholar 

  28. Misiuk W, Jozefowicz M. Study on a host–guest interaction of hydroxypropyl-β-cyclodextrin with ofloxacin. J Mol Liq. 2015;202:101–6. https://doi.org/10.1016/j.molliq.2014.12.029.

    Article  CAS  Google Scholar 

  29. Dsugi NF, Elbashir AA. Supramolecular interaction of moxifloxacin and beta-cyclodextrin spectroscopic characterization and analytical application. Spectrochim Acta A Mol Biomol Spectrosc. 2015;137:804–9. https://doi.org/10.1016/j.saa.2014.08.081.

    Article  CAS  PubMed  Google Scholar 

  30. Barbosa JS, Nolasco MM, Ribeiro-Claro P, Almeida Paz FA, Braga SS. Preformulation studies of the gamma-cyclodextrin and Montelukast inclusion compound prepared by comilling. J Pharm Sci. 2018;108:1837–47. https://doi.org/10.1016/j.xphs.2018.11.047.

    Article  CAS  PubMed  Google Scholar 

  31. Dsugi NF, Elbashir AA, Suliman FE. Supramolecular interaction of gemifloxacin and hydroxyl propyl beta-cyclodextrin spectroscopic characterization, molecular modeling and analytical application. Spectrochim Acta A Mol Biomol Spectrosc. 2015;151:360–7. https://doi.org/10.1016/j.saa.2015.06.031.

    Article  CAS  PubMed  Google Scholar 

  32. Ferreira LEN, Antunes GBM, Muniz BV, Burga-Sanchez J, de Melo NFS, Groppo FC, et al. Effects of lidocaine and the inclusion complex with 2-hydroxypropyl-beta-cyclodextrin on cell viability and proliferation of oral squamous cell carcinoma. J Pharm Pharmacol. 2018;70(7):874–82. https://doi.org/10.1111/jphp.12917.

    Article  CAS  PubMed  Google Scholar 

  33. Alves-Silva I, Sá-Barreto LCL, Lima EM, Cunha-Filho MSS. Preformulation studies of itraconazole associated with benznidazole and pharmaceutical excipients. Thermochim Acta. 2014;575:29–33. https://doi.org/10.1016/j.tca.2013.10.007.

    Article  CAS  Google Scholar 

  34. Banchero M, Ronchetti S, Manna L. Characterization of ketoprofen/methyl-β-cyclodextrin complexes prepared using supercritical carbon dioxide. J Chem. 2013;2013:1–8. https://doi.org/10.1155/2013/583952.

    Article  CAS  Google Scholar 

  35. Szabó Z-I, Deme R, Mucsi Z, Rusu A, Mare AD, Fiser B, et al. Equilibrium, structural and antibacterial characterization of moxifloxacin-β-cyclodextrin complex. J Mol Struct. 2018;1166:228–36. https://doi.org/10.1016/j.molstruc.2018.04.045.

    Article  CAS  Google Scholar 

  36. Mangolim CS, Moriwaki C, Nogueira AC, Sato F, Baesso ML, Neto AM, et al. Curcumin-beta-cyclodextrin inclusion complex: stability, solubility, characterisation by FT-IR, FT-Raman, X-ray diffraction and photoacoustic spectroscopy, and food application. Food Chem. 2014;153:361–70. https://doi.org/10.1016/j.foodchem.2013.12.067.

    Article  CAS  PubMed  Google Scholar 

  37. Abdul Rauf Khan PF, Stine KJ, D’Souza VT. Methods for selective modifications of Cyclodextrins. Chem Rev. 1998;98:1977–96.

    Article  Google Scholar 

  38. Saenger W. Cyclodextrin inclusion compounds in research and industry. Angew Chem Int Ed Engl. 1980;19:344–62.

    Article  Google Scholar 

  39. Schneider HJ, Hacket F, Rüdiger V, Ikeda H. NMR studies of Cyclodextrins and Cyclodextrin complexes. Chem Rev. 1998;98:1755–85.

    Article  CAS  Google Scholar 

  40. Tang P, Li S, Wang L, Yang H, Yan J, Li H. Inclusion complexes of chlorzoxazone with beta- and hydroxypropyl-beta-cyclodextrin: characterization, dissolution, and cytotoxicity. Carbohydr Polym. 2015;131:297–305. https://doi.org/10.1016/j.carbpol.2015.05.055.

    Article  CAS  PubMed  Google Scholar 

  41. Rao MRP, Chaudhari J, Trotta F, Caldera F. Investigation of Cyclodextrin-based nanosponges for solubility and bioavailability enhancement of rilpivirine. AAPS PharmSciTech. 2018;19(5):2358–69. https://doi.org/10.1208/s12249-018-1064-6.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We appreciated Hui Wang and Yueming Zhai from the Analytical & Testing Center of Sichuan University for helping with SEM and NMR characterization, respectively.

Funding

This work was supported by Sichuan Science and Technology Program (Grant No. 2018JY0188) and the Fundamental Research Funds for the Central Universities (Grant No. 2018SCU12043).

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Authors and Affiliations

  1. School of Chemical Engineering, Sichuan University, Chengdu, 610065, People’s Republic of China

    Xiuyun Ren, Hongyun Qian, Peixiao Tang, Yuanyuan Liu, Hongyu Pu, Man Zhang, Ludan Zhao & Hui Li

  2. National Engineering Laboratory for Clean Technology of Leather Manufacture, Sichuan University, Chengdu, 610065, People’s Republic of China

    Yuling Tang

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  1. Xiuyun Ren
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Electronic Supplementary Material

ESM 1

Fig. S1 Molecular structure of β-CD, HP-β-CD, and DM-β-CD. Fig. S2 Standard curve of BLFX. Fig. S3 Phase solubility curves of BLFX with CDs. Fig. S4 Antibacterial activity result against E. coli (a) and S. aureus (b) of pure BLFX (1), BLFX/β-CD IC (2), BLFX/HP-β-CD IC (3), BLFX/DM-β-CD IC (4) (PDF 298 kb)

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Ren, X., Qian, H., Tang, P. et al. Preparation, Characterization, and Properties of Inclusion Complexes of Balofloxacin with Cyclodextrins. AAPS PharmSciTech 20, 278 (2019). https://doi.org/10.1208/s12249-019-1425-9

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