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Advancing Rare Cancer Therapeutics: Osimertinib-Loaded Inhaled PLGA Nanoparticles for Mesothelioma Treatment
Mural Quadros1, Naveen Rajana1, Vivek Gupta2
1Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, NY, 11439, USA.
AAPS Pharmscitech
|March 3, 2026
Summary
Inhaled poly(lactic-co-glycolic acid)-osimertinib nanoparticles show promise for treating malignant pleural mesothelioma (MPM). This novel drug delivery system enhances therapeutic efficacy against MPM, offering a new strategy for this aggressive cancer.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Malignant pleural mesothelioma (MPM) has a poor prognosis and resistance to conventional treatments.
- Current therapies for MPM offer limited efficacy, with a low five-year survival rate.
- Systemic drug delivery faces challenges in effectively targeting MPM.
Purpose of the Study:
- To investigate the therapeutic potential of osimertinib (OSI) delivered via inhalation using poly(lactic-co-glycolic acid) (PLGA) nanoparticles for MPM treatment.
- To evaluate the efficacy of inhaled PLGA-OSI nanoparticles in preclinical models of MPM.
Main Methods:
- Optimized PLGA-OSI nanoparticles were formulated and characterized for encapsulation efficiency, drug loading, particle size, and zeta potential.
- In vitro cytotoxicity assays were performed on MPM cell lines (MSTO-211H, H2452, H226).
- Cellular uptake, proliferation, migration, and tumor suppression were assessed using various assays, including fluorescence microscopy, clonogenic, scratch, and spheroid models.
Main Results:
- The PLGA-OSI formulation showed favorable characteristics: 43.1% encapsulation efficiency, 4.4% drug loading, 198.5 nm particle size, and -17.6 mV zeta potential.
- In vitro studies demonstrated significant cytotoxicity against MPM cell lines with low IC50 values.
- PLGA-OSI enhanced cellular uptake, inhibited cell proliferation and migration, and showed superior tumor suppression in spheroid models compared to free OSI.
Conclusions:
- Inhaled PLGA-OSI nanoparticles represent a promising targeted drug delivery strategy for MPM.
- This approach has the potential to improve therapeutic outcomes for patients with malignant pleural mesothelioma.
- Further development of inhaled PLGA-OSI nanoparticles is warranted for MPM treatment.
