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Glioblastoma multiforme (GBM) is the most common and invasive form of malignant brain tumors and despite advances in surgery, radiotherapy, and chemotherapy, the survival of patients with GBM still remains poor. Temozolomide (TMZ) is the chemotherapy drug that is most commonly given orally after surgical resection of these tumors. In this study, the effects of solvents (i.e., dichloromethane and acetonitrile) used for the fabrication of electrosprayed TMZ-loaded poly(lactic-co-glycolic acid) (PLGA) on drug loading, loading efficiency, drug release kinetics, surface morphology, and particle size were investigated. The results from this study demonstrated that by using a larger volume of a solvent with higher polarity (i.e., acetonitrile) which allows for a higher amount of hydrophilic TMZ to dissolve into the polymer solution, higher drug loading could be achieved. However, the particles fabricated with high amount of acetonitrile, which has a lower vapor pressure, had large pores and a smaller diameter which led to an initial burst release and high cumulative release at the end of the study. An optimal combination of the two solvents is needed to result in particles with a good amount of loading and minimal initial burst release. The electrosprayed microparticles were able to illicit a cytotoxic response in U-87 MG glioblastoma cells at a lower concentration of drug compared to the free drug. This work indicated that electrospraying is a promising method for the fabrication of TMZ-loaded PLGA microparticles for the treatment of GBM and solvent composition can be altered to control drug loading and release kinetics.

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Journal of Biomedical Materials Research Part B: Applied Biomaterials





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