•  
  •  
 

Abstract

A series of new core-shell fibers were developed containing anticancer drugs (5-fluorouracil or ferulic acid) and their cyclodextrin inclusion complexes, with a gadolinium-based magnetic resonance imaging (MRI) contrast agent. These were prepared by electrospinning, a simple method for producing ultra-fine fibers through the application of a strong electrostatic force on a polymer solution. The shell of the fibers was formed from Eudragit S100, and the drugs were loaded in the core. Scanning electron microscopy images showed the formation of smooth ribbon-like fibers, with diameters ranging from 1.4 to 5.1 μm, and transmission electron microscopy reveals a transparent interface between the core and shell compartments. X-ray diffraction and differential scanning calorimetry data confirmed the encapsulation of the drug into the cyclodextrin cavity and the formation of amorphous solid dispersions in the fibers. Drug release from the systems at pH 1 and 7 showed that all the drug loading was released within one hour at pH 1. Based on these results, it is proposed that the relatively low molecular weight drugs were able to diffuse out of the system into the release medium at acidic pH, despite the insolubility of the shell polymer under these conditions. These findings have important implications for the design of electrospun drug delivery systems.

References

Aytac, Z., Sen, HS., Durgun, E. & Uyat, T. (2015). Sulfisoxazole/cyclodextrin inclusion complex incorporated in electrospun hydroxypropyl cellulose nanofibers as drug delivery system. Colloids Surf B Biointerfaces, 128, 331-338.

Aytac, Z. & Uyar, T. (2017). Core-shell nanofibers of curcumin/cyclodextrin inclusion complex and polylactic acid: Enhanced water solubility and slow release of curcumin. International Journal of Pharmaceutics, 518 (1-2), 177-184.

Aytac, Z., Calebioglu, A., Yildiz., ZI. & Uyar, T. (2018). Efficient encapsulation of citral in fast-dissolving polymer-free electrospun nanofibers of cyclodextrin inclusion complexes: High thermal stability, longer shelf-life, and enhanced water solubility of citral. Nanomaterials (Basel), 8(10)

Aytac, Z., Ipek, S, Erol, I., Durgun, E., & Uyar, T. (2019). Fast-dissolving electrospun gelatin nanofibers encapsulating ciprofloxacin/cyclodextrin inclusion complex. Colloids and Surfaces B: Biointerfaces, 1, 178, 129-136.

Akhgari, A., Heshmati, Z., Afrasiabi Garekani, H., Sadeghi, F., Sabbagh, A., Sharif Makhmalzadeh, B., & Nokhodchi, A. (2017). Indomethacin electrospun nanofibers for colonic drug delivery: In vitro dissolution studies. Colloids and Surfaces B: Biointerfaces, 152, 29–35.

Anselmi, C., Centini, M., Ricci, M., Buonocore, A., Granata,P.,Tsuno,T.,&Facino,R.M.(2006).Analytical characterization of a ferulic acid/??-cyclodextrin inclusion complex. Journal of Pharmaceutical and Biomedical Analysis, 40(4), 875–881.

Azli, A. A., Manan, N. S. A., & Kadir, M. F. Z. (2015). Conductivity and dielectric studies of lithium

trifluoromethanesulfonate doped polyethylene oxide- graphene oxide blend based electrolytes. Advances in Materials Science and Engineering, 2015(July).

Baji, A., Mai, Y. W., Wong, S. C., Abtahi, M., & Chen, P. (2010). Electrospinning of polymer nanofibers: Effects on oriented morphology, structures, and tensile properties. Composites Science and Technology, 70(5), 703–718.

Casolaro, M., Anselmi, C., & Picciocchi, G. (2005). The protonation thermodynamics of ferulic acid/γ- cyclodextrin inclusion compounds. Thermochimica Acta, 425(1–2), 143–147.

Di Donato, C., Lavorgna, M., Fattorusso, R., Isernia, C., Isidori, M., Malgieri, G., ... Iacovino, R. (2016). Alpha- and beta-cyclodextrin inclusion complexes with 5-fluorouracil: Characterization and cytotoxic activity evaluation. Molecules, 21(12).

Ghosh, S., Basak, P., Dutta, S., Chowdhury, S., & Sil, P. C. (2017). New insights into the ameliorative effects of ferulic acid in pathophysiological conditions. Food and Chemical Toxicology, 103, 41–55.

Gunn, J., & Zhang, M. (2010). Polyblend nanofibers for biomedical applications: Perspectives and challenges. Trends in Biotechnology, 28(4), 189–197.

Hu, X., Liu, S., Zhou, G., Huang, Y., Xie, Z., & Jing, X. (2014). Electrospinning of polymeric nanofibers for drug delivery applications. Journal of Controlled Release, 185(1), 12–21.

Huang, C., Chen, S., Lai, C., Reneker, D. H., Qiu, H., Ye, Y., & Hou, H. (2006). Electrospun polymer nanofibres with small diameters. Nanotechnology, 17(6), 1558– 1563.

Illangakoon, U. E., Yu, D. G., Ahmad, B. S., Chatterton, N. P., & Williams, G. R. (2015). 5-Fluorouracil loaded Eudragit fibers prepared by electrospinning. International Journal of Pharmaceutics, 495(2), 895– 902.

Inokuchi, Reina; Takaichi, H; Kawano, T. (2016). Fluorometric Quantification of Ferulic Acid Concentrations Based on Deconvolution of Intrinsic Fluorescence Spectra. Environmental Materials in Biology, 54(1), 57–64.

Jin, M., Yu, D. G., Wang, X., Geraldes, C. F. G. C., Williams, G. R., & Bligh, S. W. A. (2016). Electrospun Contrast-Agent-Loaded Fibers for Colon-Targeted MRI. Advanced Healthcare Materials, 5(8), 977–985.

Krstic, M., Radojevic, M., Stojanovic, D., Radojevic, V., Uskokovic, P., & Ibric, S. (2017). Formulation and characterization of nanofibers and films with carvedilol prepared by electrospinning and solution casting method. European Journal of Pharmaceutical Sciences. 101, 160–166.

Mancuso, C., & Santangelo, R. (2014). Ferulic acid: Pharmacological and toxicological aspects. Food and Chemical Toxicology, 65, 185–195.

Mithu, S. H., Haque, S. N., Chowdhry, B. Z., Nokhodchi, A., & Maniruzzaman, M. (2017). Evaluation of the surface chemistry and drug-polymer interaction of semi-crystalline micro-particles for the development of controlled release formulations. Materials Science & Engineering C, 76, 559–567.

Pandey, K., Dwivedi, M. M., & Tripathi, M. (2009). Structure, Interaction and Thermal Study in Electrolyte of Polyethylene Oxide/Silica/Ammonium Thiocynate Nanocomposites. Polymer Composites, 503–509.

Roy, N., Narayanankutty, A., Nazeem, P., Valsalan, R., Babu, T., & Mathew, D. (2016). Plant phenolics ferulic acid and P-coumaric acid inhibit colorectal cancer cell proliferation through EGFR down- regulation. Asian Pacific Journal of Cancer Prevention, 17(8), 4017–4021.

Samprasit, W., Akkaramongkolporn, P., & Ngawhirunpat, T. (2015). Fast releasing oral electrospun PVP / CD nano fiber mats of taste-masked meloxicam. International Journal of Pharmaceutics, 487(1–2), 213–222.

Shen, X., Yu, D., Zhu, L., Branford-White, C., White, K., & Chatterton, N. P. (2011). Electrospun diclofenac sodium loaded Eudragit® L 100-55 nanofibers for colon-targeted drug delivery. International Journal of Pharmaceutics, 408(1–2), 200–207.

Son, Y. J., Kim, W. J., & Yoo, H. S. (2014). Therapeutic applications of electrospun nanofibers for drug delivery systems. Archives of Pharmacal Research, 37(1), 69–78.

Topuz, F., & Uyar, T. (2019). Electrospinning of cyclodextrin functional nanofibers for drug delivery applications. Pharmaceutics, 11(1).

Vashisth, P., Kumar, N., Sharma, M., & Pruthi, V. (2015). Biomedical applications of ferulic acid encapsulated electrospun nanofibers. Biotechnology Reports, 8, 36– 44.

Wang, J., Cao, Y., Sun, B., & Wang, C. (2011). Characterisation of inclusion complex of trans- ferulic acid and hydroxypropyl-β-cyclodextrin. Food Chemistry, 124(3), 1069–1075.

Wang, L.-L., Zheng, W.-S., Chen, S.-H., Han, Y.- X., & Jiang, J.-D. (2016). Development of rectal delivered thermo-reversible gelling film encapsulating a 5-fluorouracil hydroxypropyl-β-cyclodextrin complex. Carbohydrate Polymers, 137, 9–18.

Wang, X., Yu, D. G., Li, X. Y., Bligh, S. W. A., & Williams, G. R. (2015). Electrospun medicated shellac nanofibers for colon-targeted drug delivery. International Journal of Pharmaceutics, 490(1–2), 384–390.

Yang, J. M., Zha, L. sheng, Yu, D. G., & Liu, J. (2013). Coaxial electrospinning with acetic acid for preparing ferulic acid/zein composite fibers with improved drug release profiles. Colloids and Surfaces B: Biointerfaces, 102, 737–743.

Zamani, M., Prabhakaran, M. P., & Ramakrishna, S. (2013). Advances in drug delivery via electrospun and electrosprayed nanomaterials. International Journal of Nanomedicine, 8, 2997–3017.

Zhang, J., Wang, X., Liu, T., Liu, S., & Jing, X. (2016). Antitumor activity of electrospun polylactide nanofibers loaded with 5-fluorouracil and oxaliplatin against colorectal cancer. Drug Delivery, 23(3), 794–800.

Zidane, S., Maiza, A., Bouleghlem, H., Herizi, W., & Dahmani, S. (2016). Investigation of Cyclodextrin Inclusion Compounds Using FT-IR, SEM and X-Ray Diffraction. International Journal of Chemical Engineering and Applications, 7(3), 182–185.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.