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. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2317–2324, 2019.

Glioblastoma (GBM) is a form of brain tumor with a low median survival rate of 16 months after diagnosis despite the many efforts to treat it. The main approach to treat GBM consists of surgery followed by radiation and chemotherapy drugs, such as Temozolomide (TMZ). However, TMZ tends to degrade fast making it hard to deliver enough amounts of the drug to the site of the tumor. The overall goal of our project is to develop a biodegradable composite system to locally deliver both an anti-angiogenic and chemotherapy agent for the treatment of glioma. The objective of this particular work was to successfully fabricate TMZ loaded biodegradable poly (lactic-co-glycolic acid) (PLGA) microparticles as carriers of the drug to protect TMZ from rapid degradation, and providing a method for controlling the release of the drug. In this study, three different methods of fabricating the microparticles were investigated and compared: single-emulsion solvent evaporation, double-emulsion solvent evaporation, and electrospraying to determine which method will result in high drug loading and sustained release of the drug. For the drug release study, 5 mg of each type of microparticle were added to 1 ml of phosphate-buffered saline (PBS) and stored and shaken in a non-CO2 incubator set at 37°C. At each time point (1, 3, 7, 10, and 14 days), the microparticles were frozen down and at the end of the study, the microparticles were dissolved in dimethyl sulfoxide (DMSO) and the drug concentration was determined by absorbance using a spectrophotometer at a wavelength of 328 nm. Compared to the two emulsion solvent evaporation methods investigated, electrospraying provides a way to fabricate TMZ loaded microparticles with a high drug loading efficiency (60% to 97% of the drug used for fabrication was loaded into the particles compared to 0.05% for the emulsion solvent evaporation methods). The lower drug loading efficiency of the emulsion solvent-evaporation technique resulted from the loss of the drug into the PVA solution during the microparticle hardening process which is avoided with the electrospraying method. The electrospraying method showed a constant controlled release of the drug over 14 days and resulted in a drug cumulative release of 90% from the microparticles at the end of the study. However, the amount of drug loaded is still low (0.72% to 1.2% of the total weight of the particles) due to the low solubility of TMZ in the solvent (i.e. dichloromethane) used for electrospraying. Thus, our future work consists of investigating other solvents to increase the amount of drug loaded. In conclusion, electrospraying is a promising method to fabricate microparticles with high drug loading efficiency and sustained release of the drug, however optimization of the solvent used to prepare the electrospraying solution is needed to increase the amount of drug loaded. Citation Format: Daniel A. Rodriguez De Anda, Sue Anne Chew. Fabrication of chemotherapy drug temozolomide-loaded poly(lactic-co-glycolic acid) microparticles by electrospraying for the treatment of glioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3719.