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

自缔合的吲哚拉明在磷脂基纳米胶束中的作用:一种潜在的抗癌纳米药物

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Abstract

This study aimed to begin development of a nanomedicine containing indisulam solubilized in sterically stabilized micelles (SSMs) composed of DSPE-PEG(2000) or sterically stabilized mixed micelles (SSMMs) composed of DSPE-PEG(2000) 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 microg/mL for SSMMs and 400 microg/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.

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