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Preparation and evaluation of inhalable dry powder containing glucosamine-conjugated gefitinib SLNs for lung cancer therapy

Abstract Gefitinib as an epidermal growth factor receptor tyrosine kinase inhibitor has strong potential in lung cancer therapy. However, a major challenge of using gefitinib is its toxicities. In the present study, we developed a dry powder inhaler dosage form containing gefitinib loaded glucosamine targeted solid lipid nanopaticles (Gef-G-SLNs) to locally transfer anticancer agent to the lung tumor. The Gef-G-SLNs were prepared by emulsion-solvent diffusion and evaporation method and optimized with irregular factorial design. The optimized nanoformulation was tested for action against A549 cells. Mannitol or lactose based dry powders were obtained from Gef-G-SLNs after spray drying and characterized using Anderson Cascade Impactor. The optimized formulation had drug loading of 33.29%, encapsulation efficiency of 97.31 ± 0.23%, zeta potential of −15.53 ± 0.47 mV, particle size of 187.23 ± 14.08 nm, polydispersity index of 0.28 ± 0.02 and release efficiency of 35.46 ± 2.25%. The Gef-G-SLNs showed superior anticancer effect compared to free gefitinib. The increased cellular uptake of G-SLNs in A549 cells was demonstrated compared with non-targeted SLNs using flow cytometry and fluorescence microscopy. The produced mannitol based microparticles showed suitable aerodynamic properties with an acceptable mass median aerodynamic diameter of 4.48 µm and fine particle fraction of 44.41%. Therefore, it can be concluded that this formulation represents promising drug delivery to treatment of lung cancer.