Liposomal formulation of model pentathiepin improves solubility and stability toward glutathione while preserving anticancer activity

The biological properties of pentathiepins have been attracting increased attention in recent years. Experiments have shown a wide range of effects of pentathiepins in vitro, such as induction of apoptosis and alteration of mitochondrial membrane potential in cancer cells, and inhibition of antioxidant enzymes, for example, glutathione peroxidase 1 (GPx1). Biological evaluation is sometimes limited due to low aqueous solubility, high lipophilicity, and poor stability toward thiols, for example, glutathione (GSH). To assess whether liposomes are suitable as drug carriers to overcome these drawbacks, a model pentathiepin was formulated in a liposomal preparation. The success of loading liposomes with pentathiepins was evaluated by using ultraviolet-visible light (UV-Vis) spectroscopy, dynamic light scattering (DLS), and high-performance liquid chromatography (HPLC). Through inclusion into 100-nm-sized 1,2-dioleoyl-sn-glycero-3-phosphocholine liposomes, the aqueous solubility of a representative pentathiepin could be increased by several orders of magnitude to ca. 400 & mu;M. The stability of the pentathiepin in the presence of GSH was increased fourfold as determined by UV-Vis spectroscopy. In antiproliferation experiments with two human cancer cell lines, no decrease in potency in the liposomal loaded pentathiepin compared to the free pentathiepin was found. In conclusion, liposomes are a suitable carrier for pentathiepins and improve both solubility and stability in the presence of thiols without compromising anticancer activity.

Automated summary

In recent years, the biological properties of pentathiepins have gained attention for their potential in cancer treatment. However, their low solubility and stability limitations have hindered biological evaluation. This study investigated the use of liposomes as drug carriers for pentathiepins to improve solubility and stability. The results showed that the aqueous solubility of pentathiepins increased significantly when incorporated into liposomes, and the stability of pentathiepins in the presence of the antioxidant glutathione was enhanced. Moreover, the liposomal loaded pentathiepins demonstrated comparable anticancer activity to free pentathiepins. In conclusion, liposomes are a suitable carrier for pentathiepins and can improve their solubility and stability without compromising their anticancer activity.