Development, characterization, and evaluation of the therapeutic efficacy of PEGylated-nanoliposomal artesunate in mice bearing non-small cell lung carcinoma.

This study focused on the development of a slow-release formulation for artesunate by PEGylated-liposome nanoparticles to improve its pharmacokinetics and antitumor properties on non-small-cell lung cancer (NSCLC) cells. The lipid-film hydration method was used to entrap artesunate in the liposomal nanoformulation coated with DSPE-mPEG(2000). The physical properties of PEGylated liposomal artesunate were characterized by the dynamic light scattering technique. Its drug release, encapsulation efficiency, and pharmacokinetics were evaluated by the HPLC analysis. It effects on the survival and the metastatic activity of NSCLC cells, the A549 cell line, were evaluated. Tumor growth inhibition and survival rate were investigated in BALB/c mice bearing NSCLC. Particle size of the PEGylated liposomal artesunate was in the nano-range (135.8 ± 8.3 nm) with a high percentage of encapsulation efficiency (93.08 ± 0.83%). It showed a sustained-release profile providing high bioavailability (Tmax: 15 min and Cmax: 166 ± 38.2 ng/ml) of artesunate in experimental mice. Pharmacokinetic analysis revealed a 14.5-fold (p < 0.05) increase in AUC0-24 and prolonged elimination half-life relative to free artesunate. In vitro studies demonstrated an improved cytotoxicity against A549 cells, reducing the IC₅₀ from 59 µg/ml and 23 µg/ml (free artesunate) to 23.4 µg/ml and 11.7 µg/ml (liposomal artesunate) at 48 h and 72 h time points, respectively. In vivo, the liposomal artesunate and free artesunate significantly delayed tumor growth, achieving a tumor growth delay of 45.7% and 18.6% respectively, with a life span prolonged by 30% and 17%, respectively, when compared to the control mice. In conclusion, encapsulation of artesunate in PEGylated liposome nanoparticles increased its bioavailability, which was accompanied by the enhanced anti-tumor activity against NSCLC in vivo.