title: 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.
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Wenhua Xi Road 107, Jinan, 250012, People's Republic of China.
authors.forename: Shilei
authors.initials: S
authors.lastname: Ni
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Fan
authors.forename: Jiangang
authors.initials: J
authors.lastname: Wang
authors.forename: Hongxu
authors.initials: H
authors.lastname: Qi
authors.forename: Xingang
authors.initials: X
authors.lastname: Li
mesh_terms: D020341:Absorbable Implants; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D005910:Glioma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology; D000077204:Temozolomide
chemical_list: D003606:Dacarbazine; D017239:Paclitaxel; D000077204:Temozolomide