Purpose
The present study aims to develop electrospun PLGA-based micro- and nanofibers as implants for the sustained delivery of anticancer drug to treat C6 glioma in vitro.
Methods
PLGA and an anticancer drug—paclitaxel-loaded PLGA micro- and nanofibers were fabricated by electrospinning and the key processing parameters were investigated. The physical and chemical properties of the micro- and nanofibers were characterized by various state-of-the-art techniques, such as scanning electron microscope and field emission scanning electron microscope for morphology, X-ray photoelectron spectroscopy for surface chemistry, gel permeation chromatogram for molecular weight measurements and differential scanning calorimeter for drug physical status. The encapsulation efficiency and in vitro release profile were measured by high performance liquid chromatography. In addition, the cytotoxicity of paclitaxel-loaded PLGA nanofibers was evaluated using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide MTT) assay on C6 glioma cell lines.
Results
PLGA fibers with diameters of around several tens nanometers to 10 μm were successfully obtained by electrospinning. Ultrafine fibers of around 30 nm were achieved after addition of organic salts to dilute polymer solution. The encapsulation efficiency for paclitaxel-loaded PLGA micro- and nanofibers was more than 90%. DSC results suggest that the drug was in the solid solution state in the polymeric micro- and nanofibers. In vitro release profiles suggest that paclitaxel sustained release was achieved for more than 60 days. Cytotoxicity test results suggest that IC50 value of paclitaxel-loaded PLGA nanofibers (36 μg/ml, calculated based on the amount of paclitaxel) is comparable to the commercial paclitaxel formulation-Taxol®.
Conclusions
Electrospun paclitaxel-loaded biodegradable micro- and nanofibers may be promising for the treatment of brain tumour as alternative drug delivery devices.
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References
Y. Dzenis. Spinning continuous fibers for nanotechnology. Science 304:1917–1919 (2004).
J. Venugopal and S. Ramakrishna. Application of polymer nanofibers in biomedicine and biotechnology. Appl. Biochem. Biotechnol. 125(3):147–158 (2005).
R. Dersch, M. Steinhart, U. Boudriot, A. Greiner, J. H. Wendorff. Nanoprocessing of polymers: applications in medicine, sensors, catalysis, photonics. Polym. Adv. Technol. 16:276–282 (2005).
B. Chu, B. S. Hsiao, D. Fang, and C. Brathwaite. Biodegradable and/or bioabsorbable fibrous articles and methods for using the articles for medical applications. US patent 6,689,374 (2004).
H. Yoshimoto, Y. M. Shin, H. Terai, and J. P. Vacanti. A biodegradable nanofiber scaffold by electrospinning and its potential for bone tissue engineering. Biomaterials 24:2077–2082 (2003).
F. Yang, R. Murugan, S. Wang, and S. Ramakrishna. Electrospinning of nano/micro scale poly(l-lactic acid) aligned fibers and their potential in neural tissue engineering. Biomaterials 26:2603–2610 (2005).
S. Y. Chew, J. Wen, E. K. F. Yim, K. W. Leong. Sustained release of proteins from electrospun biodegradable fibers. Biomacromolecules 6:2017–2024 (2005).
E. R. Kenawy, G. L. Bowlin, K. Mansfield, J. Layman, D. G. Simpson, E. H. Sanders, and G. E. Wnek. Release of tetracycline hydrochloride from electrospun poly(ethylene-co-vinylacetate), poly(lactic acid), and a blend. J. Control. Release 81:57–64 (2002).
Y. K. Luu, K. Kim, B. S. Hsiao, B. Chu, M. Hadjiargyrou. Development of a nanostrucutured DNA delivery scaffold via electrospinning of PLGA and PLA-PEG block copolymers. J. Control. Release 89:341–353 (2003).
K. Kim, Y. K. Luu, C. Chang, D. Fang, B. S. Hsiao, B. Chu, and M. Hadjiargyrou. Incorporation and controlled release for a hydrophilic antibiotic using poly(lactide-co-glycolide)-based electrospun nanofibers scaffolds. J. Controlled Release 98:47–56 (2004).
E. H. Sanders, R. Kloefkorn, G. L. Bowlin, D. G. Simpson, and G. E. Wnek. Two-phase electrospinning from a single electrified jet: microencapsulation of aqueous reservoirs in poly(ethylene-co-vinyl acetate) fibers. Macromolecules 36:3803–3805 (2003).
B. Chu, B. S. Hsiao, M. Hadjiargyrou, D. Fang, X. Zong, and K. Kim. Cell delivery system comprising a fibrous matrix and cells. US Patent 6,790,455 (2004).
X. Xu, L. Yang, X. Xu, X. Wang, X. Chen, Q. Liang, J. Zeng, and X. Jing. Ultrafine medicated fibers electrospun from W/O emulsions. J. Control. Release 108(1):33–42 (2005).
J. Zeng, X. Xu, X. Chen, Q. Liang, X. Bian, L. Yang, and X. Jing. Biodegradable electrospun fibers for drug delivery. J. Control. Release 92:227–231 (2003).
J. Zeng, L. Yang, Q. Liang, X. Zhang, H. Guan, X. Xu, X. Chen, and X. Jing. Influence of the drug compatibility with polymer solution on the release kinetics of electrospun fiber formulation. J. Control. Release 105(1–2):43–51 (2005).
S. C. Steiniger, J. Kreuter, A. S. Khalansky, I. N. Skidan, A. I. Bobruskin, and Z. S. Smimova. Chemotherapy of glioblastoma in rats using doxorubicin-loaded nanoparticles. Int. J. Cancer 109:759–767 (2004).
P. P. Wang, J. Frazier, and H. Brem. Local drug delivery to the brain. Adv. Drug Del. Rev. 54:987–1013 (2002).
M. Westphal, D. C. Hilt, and E. Bortey. A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro-oncol. 5:79–88 (2003).
J. R. Silber, M. S. Bobola, S. Ghatan, A. Blank, D. D. Kolstoe, and M. S. Berger. O 6-methylguanine-DNA methyltransferase activity in adult gliomas: relation to patient and tumor characteristics. Cancer Res. 58:1068–1073 (1998).
A. K. Singla, A. Garg, and D. Aggarwal. Paclitaxel and its formulations. Int. J. Pharm. 235:179–192 (2002).
M. A. Cahan, K. A. Walter, O. M. Colvin, and H. Brem. Cytotoxicity of Taxol in vitro against human and rat malignant brain tumours. Cancer Chemothe. Pharmacol. 33:441–444 (1994).
S. Fellner, B. Bauer, D. S. Miller, M. Schaffrik, M. Fankhanel, T. Spruh, G. Bernhardt, C. Graeff, L. Farber, H. Gschaidmeier, A. Buschsuer, and G. Fricker. Transport of Paclitaxel (Taxol) across the blood-brain barrier in vitro and in vivo. J. Clin. Invest. 10(9):1309–1317 (2002).
R. Klecker, C. Jamis-Dow, M. Egorin, K. Erkmen, R. Parker, and J. Collins. Distribution and metabolism of 3H-Taxol in the rat. Proc. Am. Assoc. Cancer Res. 34:380 (1993).
J. J. Heimans, J. B. Vermorken, J. G. Wolbers, C. M. Eeltink, O. W. M. Meijer, M. J. B. Taphoorn, and J. H. Beijnen. Paclitaxel (Taxol) concentrations in brain tumor tissue. Ann. Onc. 5:951–953 (1994).
K. A. Walter, A. C. Mitchell, A. Gur, B. Tyler, J. Hilton, O. M. Colvin, P. C. Burger, A. Domb, and H. Brem. Interstitial Taxol delivered from a biodegradable polymer implant against experimental malignant glioma. Cancer Res. 54:2207–2212 (1994).
R. B. Tishler, C. R. Geard, E. J. Hall, and P. B. Schiff. Taxol sensitizes human astrocytoma cells to radiation. Cancer Res. 52:3495–3497 (1992).
M. Bognitzki, W. Czado, T. Frese, A. Schaper, M. Hellwig, M. Steinhart. Nanostructured fibers via electrospinning. Adv. Mater. 13:70–72 (2001).
S. Megelski, J. S. Stephens, D. B. Chase, and J. F. Rabolt. Micro- and nanostructured surface morphology on electrospun polymer fibers. Macromolecules 35:8456–8466 (2002).
I. K. Kwon, S. Kidoaki, and T. Matsuda. Electrospun nano- to microfibers fabrics made of biodegradable copolyesters: structural characteristics, mechanical properties and cell adhesion potential. Biomaterials 26:3929–3939 (2005).
L. Tong, H. Wang, and X. Wang. The charge effect of cationic surfactants on the elimination of fibre beads in the electrospinning of polystyrene. Nanotechnology 15:1375–1381 (2004).
C. Dubernet. Thermoanalysis of microspheres. Thermochimica Acta 248:259–269 (1995).
G. Verreck, I. Chun, J. Peeters, J. Rosenblatt, and M. E. Brewster. Preparation and characterization of nanofibers containing amorphous drug dispersions generated by electrostatic spinning. Pharm. Res. 20(5):810–817 (2003).
O. I. Corrigan. Thermal analysis of spray dried products. Thermochim Acta 248:245–258 (1995).
T. G. Park. Degradation of poly(lactic-co-glycolic acid) microspheres: effect of copolymer composition. Biomaterials 16:1123–1130 (1995).
A. Domb, Z. H. Israel, O. Elmalak, D. Teomim, and A. Bentolia. Preparation and characterization of carmustine loaded polyanhydride wafers for treating brain tumors. Pharm. Res. 16:762–765 (1999).
S. A. Azizi and C. Miyamoto. Principles of treatment of malignant gliomas in adults: an overview. J. Neurovirol. 4(2):204–216 (1998).
P. L. Ritger and N. A. Peppas. A simple equation for description of solute release 1. Fickian and non-Fickian release from nano-swellable devices in the form of slabs, spheres, cylinders or discs. J. Controlled Release 5:23–36 (1987).
J. Xie, J. C. M. Marijnissen, and C. H. Wang. Microparticles developed by electrohydrodynamic atomization (EHDA) for the local delivery of anticancer drug to treat C6 glioma in vitro. Biomaterials 27:3321–3332 (2006).
Acknowledgments
This work is supported by the Science and Engineering Research Council, A*STAR and National University of Singapore under the grant number R279-000-208-305. The authors thank Liang Kuang Lim, Lai Yeng Lee and Dr. Yong Hu for helpful discussion and technique support.
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Xie, J., Wang, CH. Electrospun Micro- and Nanofibers for Sustained Delivery of Paclitaxel to Treat C6 Glioma in Vitro . Pharm Res 23, 1817–1826 (2006). https://doi.org/10.1007/s11095-006-9036-z
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DOI: https://doi.org/10.1007/s11095-006-9036-z