1*Gyan Vihar School of Pharmacy, Suresh Gyan Vihar University, Jaipur, Rajasthan, India. Corresponding Author. Email: khutalerohan93@gmail.com. ORCID: 0009-0000-2960-0518
2Professor, School of Pharmacy, Suresh Gyan Vihar University, Jaipur. Email: preeti.khulbe@mygyanvihar.com. ORCID: 0009-0000-3412-6961
Lung cancer remains one of the most aggressive malignancies worldwide and represents a leading cause of cancer-related mortality, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all diagnosed cases. Gefitinib, a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has demonstrated significant clinical efficacy in the management of EGFR-mutated NSCLC. However, conventional oral administration of gefitinib is associated with several pharmacokinetic limitations, including poor aqueous solubility, extensive hepatic first-pass metabolism, variable systemic bioavailability, and dose-related systemic adverse effects. Pulmonary drug delivery through dry powder inhaler (DPI) systems offers a promising strategy to overcome these limitations by enabling localized drug delivery directly to lung tissues, thereby enhancing therapeutic efficiency while minimizing systemic exposure.
The present study aimed to develop, optimize, and evaluate a gefitinib-loaded nanostructured lipid carrier (NLC)-based dry powder inhaler for targeted pulmonary drug delivery. Gefitinib-loaded NLCs were prepared using melt-emulsification followed by ultrasonication, employing Compritol 888 ATO as solid lipid, Capryol 90 as liquid lipid, and Poloxamer 188 as surfactant. The formulation variables were optimized using a Box–Behnken experimental design to achieve minimum particle size and maximum drug entrapment efficiency. The optimized NLC dispersion was subsequently converted into inhalable dry powder using spray drying with lactose monohydrate as a carrier to improve aerosolization efficiency.
The optimized NLC formulation exhibited nanoscale particle size of 182.6 ± 4.1 nm, polydispersity index of 0.276 ± 0.02, and zeta potential of −28.4 ± 2.1 mV, indicating excellent physicochemical stability. Entrapment efficiency was found to be 88.3 ± 1.9%, demonstrating efficient drug incorporation within the lipid matrix. The developed DPI showed favorable aerodynamic characteristics, including mass median aerodynamic diameter (MMAD) of 3.42 ± 0.18 μm and fine particle fraction (FPF) of 61.2 ± 2.3%, confirming its suitability for deep lung deposition. In vitro drug release studies revealed sustained drug release over 24 hours following Higuchi diffusion kinetics, indicating controlled release behavior. Stability studies confirmed the physicochemical stability of the formulation under accelerated storage conditions.
These findings demonstrate that gefitinib-loaded NLC-based DPI represents a promising targeted drug delivery system for lung cancer therapy, offering improved pulmonary deposition, sustained drug release, enhanced therapeutic efficacy, and reduced systemic toxicity compared to conventional oral therapy.
Keywords: Gefitinib, Nanostructured Lipid Carrier, Dry Powder Inhaler, Pulmonary Drug Delivery, Lung Cancer
How to cite this article: Khutale R, Khulbe P. Design, Optimization and Evaluation of Gefitinib-Loaded Nanostructured Lipid Carrier Based Dry Powder Inhaler for Targeted Pulmonary Delivery in Lung Cancer Therapy. Int J Drug Deliv Technol. 2026;16(2): 751-760. DOI: 10.25258/ijddt.16.2.80
Source of support: Nil.
Conflict of interest: None