title: Preparation and characterization of 4-dedimethylamino sancycline (CMT-3) loaded nanostructured lipid carrier (CMT-3/NLC) formulations.
abstract: Chemically modified tetracyclines (CMTs) have been reported to strongly inhibit proliferation and metastasis of various cancers, but their efficacy is restricted by poor water solubility. In the present study, a hydrophilic 4-dedimethylamino sancycline (CMT-3) loaded nanostructured lipid carrier (CMT-3/NLC) was produced by high pressure homogenization (HPH). The physical properties of CMT-3/NLC formulations were characterized by dynamic light scattering (DLS), high efficiency liquid chromatography (HPLC), atomic force microscopy (AFM), scanning electron microscopy (SEM), small-angle neutron scattering (SANS), small-angle X-ray scattering (SAXS) and wide-angle X-ray powder diffraction (XRD). The lipid and surfactant ingredients, as well as drug/lipid concentrations (m/m) were optimized to produce stable and sustained NLC formulations. In vitro cytotoxicity of CMT-3/NLC against HeLa cells was evaluated by MTT assay. The diameter of CMT-3/NLC was found to increase from 153.1±3.0 nm to a maximum of 168.5±2.0 nm after 30 days of storage, while the entrapment efficiency remained constant at >90%. CMT-3/NLC demonstrated a burst-sustained release profile in release media with different pH, a property attributed to the 3-dimensional structure of CMT-3/NLC. Cell uptake and localization studies indicated that NLC reached the cytoplasm and could thereby facilitate CMT-3 entry into HeLa cells.
authors.affiliation: State Key Laboratory of Bioreactor Engineering and Institute of Applied Chemistry, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Yang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.forename: Laszlo
authors.initials: L
authors.lastname: Almasy
authors.forename: Vasil M
authors.initials: VM
authors.lastname: Garamus
authors.forename: Aihua
authors.initials: A
authors.lastname: Zou
authors.forename: Regine
authors.initials: R
authors.lastname: Willumeit
authors.forename: Saijun
authors.initials: S
authors.lastname: Fan
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D008055:Lipids / Q000737:chemistry*; D049329:Nanostructures / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry; D013754:Tetracyclines / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; D013501:Surface-Active Agents; D013754:Tetracyclines; C117155:tetracycline CMT-3