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

Xiaomin Yang, Lin Zhao, L. Almásy, Vasil M. Garamus, Aihua Zou, Regine Willumeit, Saijun Fan

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)225-234
Number of pages10
JournalInternational Journal of Pharmaceutics
Volume450
Issue number1-2
DOIs
Publication statusPublished - Jun 25 2013

Fingerprint

Tetracyclines
Lipids
HeLa Cells
Small Angle Scattering
Powder Diffraction
tetracycline CMT-3
Atomic Force Microscopy
Neutrons
Surface-Active Agents
X-Ray Diffraction
Liquid Chromatography
Electron Scanning Microscopy
Solubility
Cytoplasm
High Pressure Liquid Chromatography
X-Rays
Neoplasm Metastasis
Pressure
Water

Keywords

  • CMT-3
  • Cytotoxicity
  • In vitro release
  • NLC
  • SANS
  • SAXS
  • XRD

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Preparation and characterization of 4-dedimethylamino sancycline (CMT-3) loaded nanostructured lipid carrier (CMT-3/NLC) formulations. / Yang, Xiaomin; Zhao, Lin; Almásy, L.; Garamus, Vasil M.; Zou, Aihua; Willumeit, Regine; Fan, Saijun.

In: International Journal of Pharmaceutics, Vol. 450, No. 1-2, 25.06.2013, p. 225-234.

Research output: Contribution to journalArticle

Yang, Xiaomin ; Zhao, Lin ; Almásy, L. ; Garamus, Vasil M. ; Zou, Aihua ; Willumeit, Regine ; Fan, Saijun. / Preparation and characterization of 4-dedimethylamino sancycline (CMT-3) loaded nanostructured lipid carrier (CMT-3/NLC) formulations. In: International Journal of Pharmaceutics. 2013 ; Vol. 450, No. 1-2. pp. 225-234.
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