Abstract
The delivery of local chemotherapy using polymeric implants is a promising anti-glioma strategy, but a high drug loading rate can lead to a problematic initial burst of drug and subsequent neurotoxicity. In this study, we designed and fabricated a biodegradable implant for the local delivery of combined paclitaxel and temozolomide (TMZ) with low drug loading rates. Paclitaxel-loaded Ca-alginate microparticles were formed using an emulsifying-solvent evaporation process. Polypropylene carbonate and different weights of TMZ were then added to the emulsion. An electrospinning process was used to form fibers that consisted of a beads-in-string structure. Using this approach, we achieved with the TMZ + paclitaxel fibers a paclitaxel loading rate of 2.1%, with a reduced initial burst of drug and prolonged release time compared to the paclitaxel-loaded microparticles alone. The TMZ loading rates of fibers with TMZ:paclitaxel ratios of 1:2, 1:1, or 2:1 (by manufacturing weight) were 1.2, 2.3, and 4.1%, respectively. A cytotoxicity assay suggested that glioma C6 cells were more sensitive to the TMZ + paclitaxel fibers compared to either agent alone. Cytotoxicity assay also showed that optimal synergistic effect was achieved when the weight ratio of the two drugs was 1:1.
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Acknowledgments
This study was financially supported by Shandong Provincial Natural Science Foundation (Grant No. Q2007C08), China Postdoctoral Science Foundation (Grant No. 20100471526), Independent Innovation Foundation of Shandong University (Grant No. 2012TS157), Shandong Provincial Outstanding Medical Academic Professional Program, and Special foundation for Taishan Scholars.
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Ni, S., Fan, X., Wang, J. et al. Biodegradable Implants Efficiently Deliver Combination of Paclitaxel and Temozolomide to Glioma C6 Cancer Cells In Vitro . Ann Biomed Eng 42, 214–221 (2014). https://doi.org/10.1007/s10439-013-0903-6
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DOI: https://doi.org/10.1007/s10439-013-0903-6