Abstract 2070: Engineered Inhalation nanoparticle formulation for lung cancer

Abstract Background: Lung cancer is a predominant cause of cancer-related morbidity and mortality across the world including in the United States. Treatment modalities for lung cancer include surgery, chemotherapy, radiotherapy, and/or targeted therapies depending on the cancer stage. Despite the survival benefits of chemotherapy, its value is offset by severe systemic side effects such as renal and/or hepatic toxicity or insufficient amounts of drug reaching to the target site. Such pitfalls can be handled by inhalable therapy which avoids first-pass metabolism and increases patients' compliance. In this study, we have investigated the inhalable therapy of cross-linked tannic acid-based nanoparticles (CTA NPs) into cancer cells and determined the synergistic effect of gambogic acid (GA) and gemcitabine (Gem). Methods: The CTA NPs formulations were characterized for particle size, chemical composition, and drug loading efficiency using various physicochemical methods (FT-IR, DSC, SEM, and TGA). Cellular uptake of CTA NPs was evaluated in lung cancer cell lines (A549 and NCI-H1299) using fluorescence microscopy and flow cytometry analysis. Further, the therapeutic efficacy of GA-Gem encapsulated CTA NPs (G-G CTA NPs) formulation was determined by various in vitro assays (CCK-8, mucoadhesion Boyden chamber, and apoptosis assays). The molecular effects of G-G CTA NPs formulation were also observed in lung cancer cell lines. Results: Our novel CTA NPs formulation provided an average size of 110 nm in dynamic light scattering with a sustained release of the drug(s). CTA NPs formulation showed a remarkable mucoadhesion and mucopenetration penetration potential in-vitro model(s). Cellular uptake studies show that CTA NPs formulation allows for effective endosomal release into the cytosol. Additionally, the G-G CTA NPs formulation showed superior in vitro anti-cancer activity in lung cancer cells (A549 and NCI-H1299) compared to free drugs. Conclusions: Taken together, our results demonstrate that G-G CTA NPs formulation exhibits superior anti-cancer potential than free drug against lung cancer and could be a novel therapeutic modality for the management of lung cancer. Citation Format: Rahul Tiwari, Eswara N. Ghali, Neeraj Chauhan, Vivek Kashyap, Subhash C. Chauhan, Murali M. Yallapu. Engineered Inhalation nanoparticle formulation for lung cancer [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 2070.