Self-associated indisulam in phospholipid-based nanomicelles: a potential nanomedicine for cancer

Abstract 

This study aimed to begin development of a nanomedicine containing indisulam solubilized in sterically stabilized micelles (SSMs) composed of DSPE-PEG₂₀₀₀ or sterically stabilized mixed micelles (SSMMs) composed of DSPE-PEG₂₀₀₀ plus egg phosphatidylcholine. Micelles were prepared by co-precipitation and reconstitution of drug and lipids. Particle size distributions of micellar formulations were determined by quasi-elastic light scattering. 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 the MCF-7 cell line by the National Cancer Institute–developed sulforhodamine B assay. Optimal solubilized indisulam concentrations in 5 mM total lipid were 10 μg/mL for SSMMs and 400 μg/mL for SSMs. HPLC results demonstrated that the encapsulation capacity of both micelles was over 95%. In vitro studies showed that indisulam in micellar system was more effective than free indisulam. The optimized formulation was successfully freeze-dried without any addition of lyoprotectants or cryoprotectants. We conclude that SSMs are a promising nanocarrier for indisulam, and indisulam-SSMs should be developed further as a novel targeted nanomedicine.

Key words: DSPE-PEG₂₀₀₀ and EPC, PEGylated phospholipids, Water-insoluble anticancer drug, Indisulam, Sterically stabilized simple micelles, Sterically stabilized mixed micelles