# Inhalable herbal nanotherapeutics targeting lung carcinoma

## TL;DR

This paper introduces an inhalable herbal therapy using nanoparticles to treat lung cancer more effectively and safely.

## Contribution

The study develops inhalable, targeted solid lipid nanoparticles of myricetin for improved lung cancer treatment.

## Key findings

- Lf-MYR-CPX-SLNs showed extended drug release and enhanced antitumor activity compared to non-targeted formulations.
- Inhalable SLN-embedded microparticles achieved efficient pulmonary deposition and limited off-target migration.
- Confocal imaging confirmed higher cellular uptake of lactoferrin-anchored nanoparticles in lung cancer cells.

## 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 (< 100 nm) allowed extended MYR release > 24 h. Superior antitumor activity of Lf-MYR-CPX-SLNs was revealed by ~ 2- and 3.5-fold reduction in IC50 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.

The online version contains supplementary material available at 10.1038/s41598-025-18460-6.