title: 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-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.
authors.affiliation: Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois 60612-7231, USA.
authors.forename: Hacer
authors.initials: H
authors.lastname: Cesur
authors.forename: Israel
authors.initials: I
authors.lastname: Rubinstein
authors.forename: Ashwini
authors.initials: A
authors.lastname: Pai
authors.forename: Hayat
authors.initials: H
authors.lastname: Onyüksel
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008823:Micelles; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry*; D012995:Solubility; D013449:Sulfonamides / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; C439829:N-(3-chloro-7-indolyl)-1,4-benzenedisulphonamide; D010743:Phospholipids; D013449:Sulfonamides