Journal
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
Volume 12, Issue 10, Pages 2474-2487Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s13346-021-01088-0
Keywords
Osimertinib; Lung cancer; Pulmonary delivery; Liposomes; Nebulization
Funding
- College of Pharmacy and Health Sciences (CPHS), St. John's University
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Inhalable OB liposomes were developed to limit systemic toxicity and locally accumulate at tumor sites. Active loading of OB into liposomes resulted in higher cytotoxicity and potential for inhibiting lung cancer growth compared to passive loading methods.
Osimertinib (OB) is a third-generation irreversible tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR), overexpressed in non-small cell lung cancer. Systemic administration of drug often results in poor drug levels at the primary tumor in the lungs and is associated with systemic side effects. In this study, we developed inhalable OB liposomes that can locally accumulate at the tumor site thereby limiting systemic toxicity. OB was loaded into liposomes via active and passive loading methods. The OB active liposomes achieved a higher encapsulation (78%) compared to passive liposomes (25%). The liposomes (passive and active) exhibited excellent aerosolization performance with an aerodynamic diameter of 4 mu m and fine particle fraction of 82%. In H1975 cells, OB active and passive liposomes reduced IC50 by 2.2 and 1.2-fold, respectively, compared to free drug. As the OB active liposomes demonstrated higher cytotoxicity compared to OB passive liposomes, they were further investigated for in vitro anti-cancer activity. The OB active liposomes inhibited tumor cell migration and colonization as determined by the scratch assay and clonogenic assay, respectively. Furthermore, the 3D spheroid studies showed that the liposomes were successful in inhibiting tumor growth. These results highlight the potential of OB liposomes to suppress lung cancer. Owing to these attributes, the inhalable OB liposomes can potentially promote better therapeutic outcomes with limited systemic toxicity.
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