Inhaled Indomethacin-Loaded Liposomes as Potential Therapeutics against Non-Small Cell Lung Cancer (NSCLC)

• Published in: Pharmaceutical research Vol. 39; no. 11; pp. 2801 - 2815
• Main Authors: Sarvepalli, Sruthi, Parvathaneni, Vineela, Chauhan, Gautam, Shukla, Snehal K., Gupta, Vivek
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.11.2022; Springer; Springer Nature B.V
• Subjects: Apoptosis; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Caspase; Cell proliferation; Cell viability; COX-2 inhibitors; Dielectric films; Drug delivery; Drug delivery systems; Drug development; Drugs; Indomethacin; Liposomes; Lung cancer; Lung cancer, Non-small cell; Lung carcinoma; Medical Law; Medical research; Medicine, Experimental; Metastases; Non-small cell lung carcinoma; Original Research Article; Pharmacology/Toxicology; Pharmacy; Physicochemical properties; Small cell lung carcinoma; Thin films; Tumors; Vehicles; COX-2 inhibition; NSCLC; caspase induction; liposomes; indomethacin
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-022-03392-x

Most lung cancer instances are non-small cell lung cancers (NSCLC). As stated by recent literature, cycloxygenase-2 (COX-2) is upregulated in lung adenocarcinomas. COX-2 relates to enhanced cell proliferation and reduced apoptosis; both of which are essential for an invasive tumor growth and metastasis. Thus, COX-2 inhibition forms an important checkpoint. Drug repurposing and nano drug delivery systems will enable the faster and more efficacious drug development. This study was designed to prepare, characterize, and establish superior effectiveness of indomethacin (IND), (a nonselective COX-2 inhibitor) as liposomes (IND-Lip). IND-Lip were made using thin film hydration method and physicochemical properties were characterized. Cell viability was performed on NSCLC cell lines (A549, H1299 and H460) Clonogenic, spheroidal, caspase and COX-2 assays were then carried out. IND-Lip were found to have optimum physicochemical properties. Based on IC 50  value of 38.4 ± 4.9 µM, A549 cells were used for further assays. From clonogenic assay, % colonies were found to be 25.5 ± 9.5% at 200 µM of IND-Lip. IND-Lip performed significantly better in ex-vivo tumor reduction in 3D spheroid assay at 200 μM concentration, compared to plain IND by Day 15. Finally, a significant inhibition of COX-2 as well as induction of caspase in all IND treated groups was observed. It is of note that liposomes demonstrated a superior efficacy in all studies compared to the plain drug. IND through liposomal delivery system can be a potentially beneficial strategy for lung carcinoma. However, further clinical studies and  in-vivo  research are essential to comprehend the complete view of this approach. Graphical abstract