NERDG 2026
Poster 13 Abstract
Advancing Rare Cancer Therapeutics: Osimertinib-Loaded Inhaled PLGA Nanoparticles as a Novel Delivery System for Mesothelioma Treatment
Mural Quadros, Naveen Rajana, Vivek Gupta
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY 11439, USA
Presenting Author: Mural Quadros
Corresponding Author: Vivek Gupta, [email protected]
Abstract
Malignant pleural mesothelioma (MPM) remains a devastating malignancy characterized by aggressive local invasion, limited treatment responsiveness, and a persistently poor prognosis, with current five-year survival rates of 12%. Conventional therapeutic strategies, including surgery, platinum-based chemotherapy, radiotherapy, and emerging immunotherapies, provide only modest benefits due to suboptimal tumor penetration, dose-limiting toxicities, and the intrinsic resistance of mesothelioma cells to systemic agents. To overcome these limitations and enhance targeted drug distribution to the pleural cavity, this study evaluates the therapeutic potential of inhaled osimertinib (OSI), a third-generation EGFR tyrosine kinase inhibitor, formulated within poly(lactic-co-glycolic acid) (PLGA) nanoparticles for localized pulmonary delivery.
An optimized PLGA-OSI nanoparticle formulation was developed using a single-emulsion solvent evaporation method, resulting in an encapsulation efficiency of 43.1 ± 4.8% and a drug loading of 4.4 ± 0.4%. The formulation was characterized by DLS to exhibit a uniform particle size of 198.5 ± 9.3 nm and a surface charge of −17.6 ± 1.2 mV. The nanosystem demonstrated favorable physicochemical stability, sustained-release characteristics, and favorable aerodynamic characteristics, such as an MMAD < 3µm and an FPF > 70%, which are key requirements for deep lung deposition. In vitro cytotoxicity studies using MTT assay revealed enhanced OSI potency across multiple mesothelioma cell lines, achieving IC₅₀ values of 13.5 ± 0.1 µM (MSTO-211H), 27.7 ± 0.3 µM (H2452), and 8.1 ± 0.2 µM (H226) at 48 h. Compared with free OSI, PLGA-OSI significantly improved cellular internalization, increasing the proportion of GFP-positive cells by 1.7-fold and total intracellular fluorescence by 5.3-fold. Assays, including clonogenic survival and scratch-wound migration, further confirmed the nanoparticle’s enhanced anti-proliferative and anti-migratory effects. Additionally, in 3D spheroid tumor models, PLGA-OSI produced pronounced growth inhibition, with multi-dose regimens yielding significant disruption and volume reduction relative to free drug controls.
Collectively, these findings demonstrate that inhalable PLGA-OSI nanoparticles not only enhance drug solubility, intracellular accumulation, and therapeutic potency but also provide a promising platform for localized, non-invasive treatment of MPM. This targeted pulmonary delivery approach has the potential to overcome key barriers associated with systemic therapy, offering a compelling strategy for improving clinical outcomes in patients with this highly refractory malignancy.
Keywords
Mesothelioma, Inhaled drug delivery, Controllled release, Nanoparticles, In vitro efficacy
Poster 13 Abstract
Advancing Rare Cancer Therapeutics: Osimertinib-Loaded Inhaled PLGA Nanoparticles as a Novel Delivery System for Mesothelioma Treatment
Mural Quadros, Naveen Rajana, Vivek Gupta
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY 11439, USA
Presenting Author: Mural Quadros
Corresponding Author: Vivek Gupta, [email protected]
Abstract
Malignant pleural mesothelioma (MPM) remains a devastating malignancy characterized by aggressive local invasion, limited treatment responsiveness, and a persistently poor prognosis, with current five-year survival rates of 12%. Conventional therapeutic strategies, including surgery, platinum-based chemotherapy, radiotherapy, and emerging immunotherapies, provide only modest benefits due to suboptimal tumor penetration, dose-limiting toxicities, and the intrinsic resistance of mesothelioma cells to systemic agents. To overcome these limitations and enhance targeted drug distribution to the pleural cavity, this study evaluates the therapeutic potential of inhaled osimertinib (OSI), a third-generation EGFR tyrosine kinase inhibitor, formulated within poly(lactic-co-glycolic acid) (PLGA) nanoparticles for localized pulmonary delivery.
An optimized PLGA-OSI nanoparticle formulation was developed using a single-emulsion solvent evaporation method, resulting in an encapsulation efficiency of 43.1 ± 4.8% and a drug loading of 4.4 ± 0.4%. The formulation was characterized by DLS to exhibit a uniform particle size of 198.5 ± 9.3 nm and a surface charge of −17.6 ± 1.2 mV. The nanosystem demonstrated favorable physicochemical stability, sustained-release characteristics, and favorable aerodynamic characteristics, such as an MMAD < 3µm and an FPF > 70%, which are key requirements for deep lung deposition. In vitro cytotoxicity studies using MTT assay revealed enhanced OSI potency across multiple mesothelioma cell lines, achieving IC₅₀ values of 13.5 ± 0.1 µM (MSTO-211H), 27.7 ± 0.3 µM (H2452), and 8.1 ± 0.2 µM (H226) at 48 h. Compared with free OSI, PLGA-OSI significantly improved cellular internalization, increasing the proportion of GFP-positive cells by 1.7-fold and total intracellular fluorescence by 5.3-fold. Assays, including clonogenic survival and scratch-wound migration, further confirmed the nanoparticle’s enhanced anti-proliferative and anti-migratory effects. Additionally, in 3D spheroid tumor models, PLGA-OSI produced pronounced growth inhibition, with multi-dose regimens yielding significant disruption and volume reduction relative to free drug controls.
Collectively, these findings demonstrate that inhalable PLGA-OSI nanoparticles not only enhance drug solubility, intracellular accumulation, and therapeutic potency but also provide a promising platform for localized, non-invasive treatment of MPM. This targeted pulmonary delivery approach has the potential to overcome key barriers associated with systemic therapy, offering a compelling strategy for improving clinical outcomes in patients with this highly refractory malignancy.
Keywords
Mesothelioma, Inhaled drug delivery, Controllled release, Nanoparticles, In vitro efficacy
