Biodegradable Implants Efficiently Deliver Combination of Paclitaxel and Temozolomide to Glioma C6 Cancer Cells In Vitro

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.