NERDG 2026
Poster 24 Abstract
Fabricating Inhalable PLGA Nanoparticles for Targeted Therapy in Non-small Cell Lung Cancer
Apoorva Daram, Parasharamula Kommarajula, Druvasarika Rongala, Ruginn Catarata, Nitesh K. Kunda
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY 11439, USA
Presenting Author: Parasharamula Kommarajula
Corresponding Author: Nitesh Kunda, [email protected]
Purpose
Lung cancer remains a leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) comprising over 80% of cases. Targeted therapies, particularly epidermal growth factor receptor (EGFR) inhibitors, have significantly improved outcomes for NSCLC patients with EGFR overexpression. However, prolonged use of these inhibitors often leads to drug resistance and activation of alternative signaling pathways. Recently, the investigational agent INA has demonstrated potent anticancer efficacy. In this study, INA was encapsulated in polymeric nanoparticles and spray-dried into an inhalable dry powder for pulmonary delivery, enabling localized drug targeting to the lungs while minimizing systemic toxicity.
Methods
PLGA nanoparticles (INA PLGA NPs) were prepared by dissolving PLGA and INA in dichloromethane (DCM), followed by addition to a 2.5% PVA solution and probe sonication. The dispersion was transferred to 0.75% PVA, and DCM was evaporated. The resultant INA PLGA NPs were spray-dried with L-leucine to obtain dry powder (SD-INA). INA PLGA NPs and SD-INA were characterized for particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), and drug loading (DL). Solid-state properties and aerosolization of SD-INA were studied using DSC and NGI, respectively. Cytotoxicity of INA and INA PLGA NPs was evaluated by MTT assay in A549 cells.
Results
INA PLGA NPs showed a particle size of 224.19 ± 23 nm, PDI of 0.21 ± 0.04, and ZP of –15.13 ± 3.45 mV. The encapsulation efficiency and drug loading were 81.49 ± 7.91% w/w and 35.68 ± 0.64 μg/mg polymer. SD-INA had a yield of 44.40 ± 4.59% and drug loading of 33.93 ± 4.65 μg/mg. DSC and PXRD confirmed INA entrapment within the polymer. NGI data indicated deposition between Stages 3 and 7, representing the lower respiratory tract, with a MMAD of 2.29 ± 0.16 µm and a FPF of 81.32 ± 2.89% w/w. INA and INA PLGA NPs showed IC50 of 0.44 ± 0.01and 0.46 ± 0.02 µM, respectively, in A549 cells, indicating potent anticancer activity.
Conclusion
Overall, this study demonstrates the successful development of inhalable INA-loaded PLGA nanoparticles, which can be a promising approach for targeted therapy in non-small cell lung cancer.
Keywords
Inhalable PLGA Nanoparticles, Targeted Therapy, epidermal growth factor receptor (EGFR) inhibitors, NSCLC
Poster 24 Abstract
Fabricating Inhalable PLGA Nanoparticles for Targeted Therapy in Non-small Cell Lung Cancer
Apoorva Daram, Parasharamula Kommarajula, Druvasarika Rongala, Ruginn Catarata, Nitesh K. Kunda
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY 11439, USA
Presenting Author: Parasharamula Kommarajula
Corresponding Author: Nitesh Kunda, [email protected]
Purpose
Lung cancer remains a leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) comprising over 80% of cases. Targeted therapies, particularly epidermal growth factor receptor (EGFR) inhibitors, have significantly improved outcomes for NSCLC patients with EGFR overexpression. However, prolonged use of these inhibitors often leads to drug resistance and activation of alternative signaling pathways. Recently, the investigational agent INA has demonstrated potent anticancer efficacy. In this study, INA was encapsulated in polymeric nanoparticles and spray-dried into an inhalable dry powder for pulmonary delivery, enabling localized drug targeting to the lungs while minimizing systemic toxicity.
Methods
PLGA nanoparticles (INA PLGA NPs) were prepared by dissolving PLGA and INA in dichloromethane (DCM), followed by addition to a 2.5% PVA solution and probe sonication. The dispersion was transferred to 0.75% PVA, and DCM was evaporated. The resultant INA PLGA NPs were spray-dried with L-leucine to obtain dry powder (SD-INA). INA PLGA NPs and SD-INA were characterized for particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), and drug loading (DL). Solid-state properties and aerosolization of SD-INA were studied using DSC and NGI, respectively. Cytotoxicity of INA and INA PLGA NPs was evaluated by MTT assay in A549 cells.
Results
INA PLGA NPs showed a particle size of 224.19 ± 23 nm, PDI of 0.21 ± 0.04, and ZP of –15.13 ± 3.45 mV. The encapsulation efficiency and drug loading were 81.49 ± 7.91% w/w and 35.68 ± 0.64 μg/mg polymer. SD-INA had a yield of 44.40 ± 4.59% and drug loading of 33.93 ± 4.65 μg/mg. DSC and PXRD confirmed INA entrapment within the polymer. NGI data indicated deposition between Stages 3 and 7, representing the lower respiratory tract, with a MMAD of 2.29 ± 0.16 µm and a FPF of 81.32 ± 2.89% w/w. INA and INA PLGA NPs showed IC50 of 0.44 ± 0.01and 0.46 ± 0.02 µM, respectively, in A549 cells, indicating potent anticancer activity.
Conclusion
Overall, this study demonstrates the successful development of inhalable INA-loaded PLGA nanoparticles, which can be a promising approach for targeted therapy in non-small cell lung cancer.
Keywords
Inhalable PLGA Nanoparticles, Targeted Therapy, epidermal growth factor receptor (EGFR) inhibitors, NSCLC
