Abstract/Summary

Background: NSCLC is the most common type of lung cancer, making up 85% of all lung cancer cases. One of the primary challenges is the difficulty in early detection, leading to low survival rates. Respiratory infections can damage cells, impair lung function, and hinder lung cells from destroying cancer cells. Such infections complicate 50-70% of cancer cases and cause immunosuppression, preventing the immune system from effectively combating cancer. Additionally, chronic lung tissue inflammation can progress into cancer. Lung cancer is often accompanied by secondary infections and inflammation related to the cancer itself. Aim: To improve the therapeutic effectiveness of treatments for NSCLC and respiratory infections, addressing the primary challenge of limited drug targeting, suboptimal bioavailability, and systemic toxicity. Our focus was on investigating innovative strategies through particle engineering in pulmonary drug delivery to provide more tailored solutions for effective treatments. Methods: This thesis investigated the development and evaluation of lipid nanoparticles produced using the microemulsion technique, subsequently transformed into powders through spray drying. Additionally, it explored the development of spray-dried microparticles utilizing the two and three fluid nozzle configurations, loaded with one or two repurposed drugs—pimozide, hydroxychloroquine, or rifaximin—to target NSCLC and related infections and inflammations. The thesis evaluated their physical stability, chemical integrity, functional performance, and in vitro efficacy. Results & Conclusion: Pimozide-loaded nanostructured lipid carriers (NLCs) outperformed solid lipid nanoparticles (SLNs) and liquid lipid carriers (LLCs) with higher encapsulation efficiency, potential cytotoxicity against A549 lung cancer cells, and a biphasic drug release profile. NLCs with pimozide and hydroxychloroquine showed synergistic antiproliferative and anti-inflammatory effects. Microparticles made with the three-fluid nozzle method had better recovery percentages, customized release profiles, and enhanced activities compared to the two-fluid nozzle method. Microparticles with hydroxychloroquine and rifaximin, prepared using the three-fluid nozzle, exhibited superior antiproliferative, anti-inflammatory, and antimicrobial effects against drug-resistant A. baumannii.