%0 journal article
%@ 0378-5173
%A Yang, X.,Zhao, L.,Almasy, L.,Haramus, V.M.,Zou, A.,Willumeit, R.,Fan, S.
%D 2013
%J International Journal of Pharmaceutics
%N 1-2
%P 225-234 
%R doi:10.1016/j.ijpharm.2013.04.021
%T Preparation and characterization of 4-dedimethylamino sancycline (CMT-3) loaded nanostructured lipid carrier (CMT-3/NLC) formulations
%U https://doi.org/10.1016/j.ijpharm.2013.04.021
1-2 
%X 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.