Abstract Targeted cancer therapy promises high local drug exposure, superior efficacy and minimal hazards. Myricetin (MYR) flavonoid exhibits distinct apoptotic and antiproliferative effects on lung carcinoma. However, limited solubility and bioavailability restricted its biomedical application. Attempt for dual targeting relies on the development of receptor-mediated solid lipid nanoparticles (SLNs) and inhalation therapy. Inhalable powder was compared to non-targeted IV-administered nanocarriers. SLNs loaded with myricetin-phospholipid-complex (MYR-PH-CPX) were anchored with lactoferrin (Lf). The physicochemical properties, antitumor activity and cellular uptake were investigated. Inhalable SLN-embedded microparticles (MPs) were spray-dried, and the aerosolization parameters were determined. In-vivo deposition and biodistribution of targeted and non-targeted coumarin-labelled SLNs (Cou-SLNs ± Lf) were studied in mice. Lf-MYR-CPX-SLNs ( 24 h. Superior antitumor activity of Lf-MYR-CPX-SLNs was revealed by ~ 2- and 3.5-fold reduction in IC 50 relative to MYR-CPX-SLNs and MYR-PH-CPX, respectively. Confocal imaging showed higher rate and extent of uptake of Lf-Cou-SLNs in A549-cells. MYR-SLN-embedded MPs were suited for bronchial deposition (MMAD 2.81 µm, FPF 80.5%), while Lf-Cou-SLNs-MPs ensured 1.5-fold in-vivo pulmonary deposition and limited migration to other body organs relative to IV-administered counterparts. The developed targeted inhalation therapy achieved efficient anti-tumor effect, targetability, preferential pulmonary deposition and low off-target biodistribution, which augmented the safety threshold.
Gaber et al. (2026) studied this question.