Preparation and characterization of stable nanoliposomal formulations of curcumin with high loading efficacy: In vitro and in vivo anti-tumor study

Abstract

Liposomal formulations were made using Solvent-assisted active loading technology (SALT). Two formulations composed of HSPC:DPPG:Chol:DSPE-mPEG₂₀₀₀ (PG-LipCUR) and HSPC:Chol:DSPE-mPEG₂₀₀₀ (LipCUR) demonstrated good colloidal properties and the CUR-encapsulation of 82% and 89% for PG-LipCUR and LipCUR, respectively. The results showed that both formulations were stable during 6 months storage at 4 °C. The release study showed that the PG-LipCUR and LipCUR formulations are relatively stable at pH 7.4. Both formulations had higher cytotoxicity on TUBO and 4T1 cell lines in compassion with normal cells. PG-LipCUR had the higher amounts of CUR cellular uptake than LipCUR. Biodistribution studies showed that both formulations could enhance the half-life of the CUR 2-3 times compared to free CUR. The tumor accumulation of PG-LipCUR was significantly higher than LipCUR. The antitumor activities of liposomes on 4T1 tumor model demonstrated the efficacy of both formulations compared to PBS and free CUR. PG-LipCUR also was more potent in tumor growth delay in comparison with LipCUR. However, combination of the Caelyx® and PG-LipCUR had the most antitumor properties among other treatments. Based on the results, PG-LipCUR could be a promising formulation for the delivery of CUR which also significantly increased the efficacy of Caelyx® and merits further investigation.

Keywords: Antitumor activity; Biodistribution; Cancer drug delivery; Curcumin; Liposome.