Abstract 5755: Development of paclitaxel-loaded nanoparticles with high charge density

Abstract

Abstract Paclitaxel (PTX) is a potent anticancer agent with desirable efficacy against pancreatic cancer when used in conjunction with gemcitabine. The current formulation of nab-paclitaxel shows an improved safety profile compared to the conventional PTX, but the highly potent nature of paclitaxel still poses a problem as it leads to severe side effects, such as neutropenia and neuropathy, calling for the development of carriers with better targeting ability. Tumor treating fields (TTFields) is a new noninvasive treatment modality which disrupts the mitosis of a cell with alternating electric fields with low and intermediate frequency (100 - 500 kHz). Highly polar or charged macromolecules are impacted by the presence of TTFields as they lose random motions essential for mitosis. In previous work on the formulation of self-assembling cationic-anionic nanoparticles (S-CAP NPs), gemcitabine was successfully loaded into the nanoparticles with optimal particle size, stability, and release profile responsive to TTFields. In this study, S-CAP NPs were developed with biocompatible polymers, DEAE-dextran (Ddex) and bovine serum albumin (BSA), via a relatively green method to load paclitaxel with minimal use of organic solvents. Based on the previous study and the proof of concept, it can be hypothesized that the S-CAP NPs can successfully carry PTX and release it in the presence of TTFields. Various parameters, such as temperature, rpm, and concentration, were tested to optimize the size, PDI, zeta potential, and stability of the particles. The HPLC method was developed for PTX and used to analyze drug loading. Numerous compositions of BSA and Ddex were tested, and the ratio of 10:1 (BSA:Ddex) developed the best parameters of the S-CAP NPs. At 50 °C, the zeta potential of the particle was -3.55 ± 0.23 mV for the NPs, but the particles agglomerated over time as BSA precipitates were formed. At -15°C, the particle size was 302.9 ± 2.0 nm (PDI = 0.307 ± 0.038). Varying concentrations of BSA and Ddex showed the formation of S-CAP NPs at lower concentration. The optimal particle was formed at room temperature (RT) with BSA 0.1% and Ddex 0.01% with a size of 264.6 ± 19.7 nm (PDI = 0.079 ± 0.028) and a zeta potential of -14.67 ± 0.07 mV. The particles showed desirable stability for 48 hours. The HPLC analysis (Agilent, Phenomenex C18, 150 x 4.6 mm, 5 micron) was tested for validity and robustness (r2 = 0.9996). Currently, the drug loading was achieved at 1.9% and the optimization studies are ongoing. In vitro cell viability assay (MTS) with and without TTFields is under exploration. With the successful formulation of PTX-loaded S-CAP NPs, co-loading PTX and gemcitabine can be explored to reduce the treatment burden of the patients. Citation Format: Katherine Y. Bang, Preshita P. Desai. Development of paclitaxel-loaded nanoparticles with high charge density [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 5755.