文献类型：期刊文献

英文题名：Preparation and characterization of 4-dedimethylamino sancycline (CMT-3) loaded nanostructured lipid carrier (CMT-3/NLC) formulations

作者：Yang, Xiaomin[1,2];Zhao, Lin[4];Almasy, Laszlo[5];Garamus, Vasil M.[3];Zou, Aihua[1,2];Willumeit, Regine[3];Fan, Saijun[4]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]E China Univ Sci & Technol, Inst Appl Chem, Shanghai 200237, Peoples R China;[3]Helmholtz Zentrum Geesthacht, Ctr Mat & Coast Res, Inst Mat Res, D-21502 Geesthacht, Germany;[4]Soochow Univ, Sch Radiat Med & Protect, Coll Med, Suzhou 215123, Peoples R China;[5]Wigner Res Ctr Phys, Inst Solid State Phys & Opt, H-1525 Budapest, Hungary

年份：2013

卷号：450

期号：1-2

起止页码：225

外文期刊名：INTERNATIONAL JOURNAL OF PHARMACEUTICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000319444300025)】；

基金：We would like to express our gratitude to Prof. Leonard I Wiebe for thoughtful discussions. Daniel Laipple is acknowledged for help during SEM measurements. Ai-hua Zou gratefully acknowledges the support of this work by the Alexander von Humboldt Foundation. We gratefully acknowledge the support of this work by the Chinese National Natural Science Foundation (201003047), Fundamental Research Funds for the Central Universities (WK1014024), and Innovation Program for Graduate Students of Jiangsu Province (CXZZ12_0832). SANS measurements have been performed under the support of the European Commission (Grant agreement N 226507-NMI3).

语种：英文

外文关键词：NLC; CMT-3; SANS; SAXS; XRD; In vitro release; Cytotoxicity

摘要：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. (C) 2013 Elsevier B.V. All rights reserved.