Abstract 1744: Injectable alginate scaffolds for the dual delivery of Minocycline and Temozolomide for the treatment of glioblastoma

Abstract

Abstract Glioblastoma Multiforme (GBM) is the most frequent and aggressive malignant primary brain tumor in adults with a life expectancy of less than fifteen months after diagnosis. The standard care for GBM includes surgical resection followed by radiotherapy and chemotherapy. Despite advances in the different methods of therapy, the prognosis for gliomas has not been dramatically improved through the years due to high levels of reoccurrence therefore, alternative treatment methods are needed for GBM. Minocycline (MINO) is a common antibiotic with potential anticancer effects by acting as an anti-angiogenic agent which can help in the treatment and reduction of gliomas by reducing blood vessel formation. Temozolomide (TMZ) is a chemotherapy alkylating agent that has demonstrated antitumor activity against highly resistant malignancies as high-grade gliomas. Injectable alginate scaffolds can serve as a local delivery system for controlled drug release and can be an important component for the development of a treatment method against GBM. The objective of this study was to investigate the optimal concentration of TMZ and MINO alone or in combination against glioblastoma cells (U87-MG) and human umbilical vein endothelial cells (HUVEC) and to evaluate the ability of an injectable alginate scaffold to control the rate of drug release for the treatment of GBM. In this study, U87-MG were treated with MINO (0-4000 µM) and TMZ (0-6000 µM), while HUVEC were treated with MINO (0-1000 µM) and TMZ (0-2000 µM) alone or in combination and a MTT assay was used to determine cell viability. Injectable alginate scaffolds were fabricated by dissolving sodium alginate and calcium carbonate in water and then homogenized with glucanolactone and drugs for 20 seconds. The mixture was then injected into a 24-well plate. After fabrication, scaffolds with MINO, TMZ and MINO/TMZ were incubated in PBS at 37 °C. At each timepoint (1, 4, 7, 10 and 14 days), the amount of drug released was measured by reading the absorbance of MINO and TMZ at 350 and 327 nm, respectively using a microplate reader. The 50% inhibitory concentration (IC50) of MINO and TMZ were found to be 950 µM and 900 µM, respectively in U87-MG. In HUVEC, the IC50 of MINO and TMZ were found to be 150 µM and 400 µM, respectively. MINO and TMZ alone reduced cell viability by 39% and 41%, respectively, in U87-MG and in HUVEC by 36% and 34%, respectively. In combination, both drugs reduced cell viability in U87-MG by 58% and in HUVEC by 56%, resulting in synergistic effects for both cell lines. In addition, the application of the injectable alginate scaffold resulted in a controlled release of the drugs alone or in combination. In conclusion, the combination of MINO and TMZ resulted in synergistic effects on cell viability in both cell lines and the controlled delivery of both drugs with an injectable scaffold can be a promising method for the treatment of GBM. Citation Format: Marco A. Arriaga, Rene N. Rico, Kaitlyn D. Ybanez, Daniela Lopez-Lorenzo, Sue Anne Chew. Injectable alginate scaffolds for the dual delivery of Minocycline and Temozolomide for the treatment of glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1744.