SELF-ASSOCIATED INDISULAM IN PHOSPHOLIPID-BASED NANOMICELLES: A POTENTIAL NANOMEDICINE FOR CANCER

摘要

This study aims to start the development of a nanomedicine, containing indisulam solubilized in sterically stabilized micelles (SSM) composed of DSPE-PEG2000 or sterically stabilized mixed micelles (SSMM) composed of DSPE-PEG2000 plus egg phosphatidylcholine (EPC). Micelles were prepared by coprecipitation and reconstitution of drug and lipids. Particle size distributions of micellar formulations were determined by quasi-elastic light scattering (QELS). Amounts of solubilized drug were determined by Reverse Phase-High Performance Liquid Chromatography (RP-HPLC). In vitro cytotoxicity of indisulam in nanocarrier was determined on MCF-7 cell line by NCI developed Sulforhodamine B assay. Optimal solubilized indisulam concentrations in 5mM total lipid were 10 µg/ml for SSMM, and 400 µg/ml for SSM. HPLC results demonstrated encapsulation capacity of both micelles was over 95%. In vitro studies showed indisulam in micellar system was more effective than free indisulam. Optimized formulation was successfully freeze-dried without any addition of lyo- and cryo-protectants. We conclude SSM is a promising nanocarrier for indisulam, and indisulam-SSM should be developed further as a novel targeted nanomedicine.