Abstract 2000: Injectable alginate scaffolds for the delivery of minocycline for the treatment of glioblastoma

Abstract

Abstract Glioblastoma Multiforme (GBM) is a Grade IV malignant brain cancer that is associated with a high recurrence and low survival rate amongst affected patients. Despite advances in the different methods of therapy, the prognosis for GBM has not improved through the years and, thus, alternative treatment methods for GBM are needed. Minocycline (MINO) is known as a semi-synthetic tetracycline that serves as an antibiotic and has also been shown to be able to suppress angiogenesis for GBM treatment. Collected from brown seaweed, alginate is a biodegradable polysaccharide that can be used to form a hydrogel for drug delivery due to its biocompatibility properties. Injectable alginate scaffolds may be a promising component for an adjuvant treatment method against GBM as the injectability property of the scaffold will allow for the site of interest to be filled precisely after tumor resection. The objective of this study is to develop injectable alginate scaffolds for the delivery of MINO for the treatment of GBM. The effects of the concentration of sodium alginate (SA) and calcium carbonate (CaCO3) (i.e., 0.75, 1.00, 1.50, and 2.00 wt./vol.%) with a 0.25 wt./vol.% of glucono-delta lactone (GDL) on the pH, gelation time, dimensions, degradation, and drug release kinetics of alginate scaffolds were investigated. Injectable alginate scaffolds were fabricated by dissolving SA and CaCO3 (1:1) in water, homogenized with GDL for 20 sec., and then injected into a 24-well plate to develop uniform scaffolds. Their properties were evaluated by testing pH values via a pH meter, timing gelation with a digital timer, utilizing a digital microcaliper to investigate dimensions, an analytical scale to evaluate the mass of dried scaffolds to determine scaffold degradation, and evaluating the release rate of MINO using a microplate reader at a wavelength of 350 nm. As the concentration of SA and CaCO3 increased, an increase in pH, gelation time, and overall stability of the scaffold were observed. All four concentrations of SA and CaCO3 tested resulted in scaffolds with desired pH and workable gelation time; however, the 1 wt./vol.% group may be the most ideal as an optimal pH was reached after 10 minutes and the gelation time for these scaffolds was ~8 minutes. Lower concentration scaffolds (0.75 and 1.00 wt./vol.%) degraded faster in comparison to those made with higher concentrations. Drug release kinetics data revealed that the scaffolds can sustain short term release but could be improved by incorporating the drug into micro or nanoparticles before incorporation into the scaffolds. In conclusion, the injectable alginate scaffolds developed in this study may be promising biomaterials for the delivery of drugs for GBM treatment. Citation Format: Kaitlyn D. Ybáñez, Marco A. Arriaga, Rene N. Rico, Theresia Rookstool, Sue Anne Chew. Injectable alginate scaffolds for the delivery of minocycline for the treatment of glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2000.