Akademik Veri Yönetim Sistemi
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, cilt.121, 2026 (SCI-Expanded, Scopus)
Non-small cell lung cancer (NSCLC) remains difficult to treat due to systemic toxicities, poor tumor uptake and the development of resistance to immunotherapies and novel molecular targeted therapies, including oral tyrosine kinase inhibitors. We aimed to develop an inhalable lyophilized dry powder of gefitinib-loaded human serum albumin (HSA) nanoparticles, coated with hyaluronic acid for tumor targeting. Various carriers were evaluated for incorporation of nanoparticles into lyophilized dry powder inhalers (DPIs) with aerodynamic diameters between 1 and 5 mu m for deep lung deposition. The phenylalanine-mannitol combination delivered optimal aerosol performance and sustained in vitro release over 72 h. Formulation within HSA nanoparticles and subsequent lyophilization converted crystalline gefitinib into a high-surface-area amorphous form, markedly enhancing its aqueous solubility. In vitro, MTT assays in Lewis Lung Carcinoma-1 (LLC1) cells demonstrated a significant reduction in cell viability at lower doses compared with raw gefitinib, and flow cytometry confirmed efficient uptake of Nile red-loaded DPIs. In an orthotopic murine lung cancer model, a single inhaled dose achieved prolonged pulmonary retention, induced apoptosis, minimized systemic toxicity, and produced marked tumor regression. Pharmacokinetic studies in rats showed slower clearance and detectable gefitinib levels in the lungs up to 96 h post-administration. These inhalable lyophilized Gefitinib-HSA DPIs offer sustained lung delivery and potent antitumor activity, representing a promising targeted therapy for NSCLC.