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.

Anti-Neoplastic Cytotoxicity of SN-38-Loaded PCL/Gelatin Electrospun Composite Nanofiber Scaffolds against Human Glioblastoma Cells In Vitro

“…However, the application of the BCNU‐loaded polyanhydride wafer as a drug vehicle has been limited by significant drawbacks, including its rigidness and rapid drug release rate, as well as a series of complications in patients, such as seizures, cerebral edema, infection, and abnormal wound healing . In a previous study, we manufactured a biodegradable implant containing paclitaxel and temozolomide for local drug delivery using an electrostatic spinning method, and showed that our implant provided more stable drug release and a longer release time in comparison with paclitaxel‐loaded microspheres alone …”

“…6,7 In a previous study, we manufactured a biodegradable implant containing paclitaxel and temozolomide for local drug delivery using an electrostatic spinning method, and showed that our implant provided more stable drug release and a longer release time in comparison with paclitaxel-loaded microspheres alone. 8 Numerous natural and synthetic polymers are considered potentially useful in tissue engineering applications and as biodegradable drug delivery carriers. PCL-gelatin (GT) composite materials are widely used in tissue engineering and controlled drug delivery because of their good biocompatibility and mechanical, physical, and chemical properties.…”

The proteomic landscape of glioma stem-like cells

“…Given these results, SYMPK might prove to be a useful target in the design of a novel chemotherapy-based treatment strategy for GBM. The commonly accepted treatment protocol for GBM involves surgical resection, followed by chemotherapy treatment (usually with TMZ as adjuvant chemotherapy), and radiation [6], but a recent study has demonstrated the effectiveness of combination therapies using TMZ and paclitaxel [64]. Another study, using paclitaxel poliglumex in combination with TMZ and concurrent radiation, showed some promise in terms of overall survival, but the drugs could not be combined safely due to toxicity issues [65].…”

Reduced graphene oxide‐based electrochemically stimulated method for temozolomide delivery

“…TMZ is an alkylating agent; these alkylating species inhibits DNA replication by delivering a methyl group to purine bases of DNA (N7-guanine, O6-guanine and N3-adenine) (Zhang, Stevens, & Bradshaw, 2012). TMZ drug is a fast degradable and short plasma half-life of 1.8 hr, encapsulation of TMZ drug into nanomaterials can be advantageous to attain the controlled, stable and sustained release of the TMZ drug for inhibition of tumour cells growth, several nanomaterials have been studied, which were listed in the Table 1 (Akbar et al, 2009;Fang et al, 2015;Fourniols et al, 2015;Huang, Lin, Wen, Gu, & Zhao, 2016;Irani, Sadeghi, & Haririan, 2018;Irani et al, 2017aIrani et al, , 2017bKumari, Ahsan, Kumar, Kondapi, & Rao, 2017; Lanz-Landázuri, Portilla-Arias, Martínez de Ilarduya, García-Alvarez, & Holler, 2014;Ni, Fan, Wang, Qi, & Li, 2014;Ramachandran et al, 2017;Scott et al, 2011;Tavakoli et al, 2017;Xu, Shen, et al, 2016;Zhang & Gao, 2007;Zheng, Wang, Liu, Xie, & Deng, 2018). In addition, the advantage of local delivery of TMZ drug as compared with oral administration has been shown in rodent glioblastoma models (Ni et al, 2014;Brem et al, 2007).…”