Abstract 5745: Electrosprayed minocycline and temozolomide-loaded PLGA microparticles for the treatment of glioblastoma

Abstract

Abstract Glioblastoma multiforme (GBM), the most common and aggressive form of malignant brain tumor, leads to poor prognoses with high rates of reoccurrence and low survival rates, therefore, it is vital to explore alternative treatments for GBM. Minocycline, a commonly used antibiotic and tetracycline derivative, has proven anti-angiogenic effects and the ability to inhibit tumor growth, making it an effective GBM treatment. Temozolomide is an alkylating antineoplastic agent and the current first-choice chemotherapy agent for GBM. Poly(lactic-co-glycolic acid) (PLGA) is widely used as a biomaterial for drug delivery due to its inert properties, great biocompatibility and versatility and has been approved by the FDA. Therefore, the objective of this project is to fabricate electrosprayed minocycline- and temozolomide-loaded PLGA microparticles with optimal morphology, drug loading, loading efficiency, and drug release kinetics for the treatment of GBM. The microparticles were fabricated by electrospraying vertically with a 2ml/hr flow rate, 14kV voltage, 20 cm distance for minocycline and a 10ml/hr flow rate, 10kV voltage, 10 cm distance for temozolomide with both collected on a copper/glass plate. The parameters that were investigated were the chamber humidity, duration of spraying, and the addition of polyethylene glycol (PEG), a hydrophilic polymer. To determine the microparticles’ morphology, bright-field microscopy and scanning electron microscopy (SEM) were used. The absorbance measurements at 350 and 327 nm were used to determine drug loading, loading efficiency, and release kinetics for minocycline and temozolomide, respectively. Microparticles with low chamber humidity and duration of spraying were more spherical, less aggregated and easier to collect for both drugs. The addition of PEG to minocycline-loaded microparticles led to higher drug loading and loading efficiency (4.02% ± 0.34, 64.30% ± 5.47 vs. 3.23% ± 0.29, 49.40% ± 4.49) as the PEG helps the solubilization of minocycline. Using acetonitrile instead of dichloromethane as the solvent, increased drug loading and loading efficiency (4.72% ± 0.76, 70.77 ± 11.43 vs. 2.37% ± 0.27, 35.62% ± 4.09) for temozolomide-loaded microparticles as more temozolomide can be solubilized in acetonitrile. Drug release kinetics demonstrated a burst release of minocycline in the first hour (65.46%). To decrease the burst release, the microparticles can be incorporated into a scaffold or depot. Overall, electrospraying is a promising method to fabricate drug loaded PLGA microparticles with high drug loading, loading efficiency, and right morphology and we determined optimal parameters to successfully fabricate electrosprayed drug loaded PLGA microparticles in the micron size range with high drug loading and loading efficiency compared to the often-used emulsion solvent extraction/evaporation for microparticle fabrication. Citation Format: Alma Rodriguez, Jaqueline Quintanilla, Juan Amieva, Marco A. Arriaga, Sean Nievera, Ivan Davila, Karen S. Martirosyan, Sue Anne Chew. Electrosprayed minocycline and temozolomide-loaded PLGA microparticles for the treatment of glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5745.