Structural characterization of novel gemini non-viral DNA delivery systems for cutaneous gene therapy

摘要

The structural and physicochemical properties of novel cationic lipid-based DNA complexes have been investigated for the purpose of designing microano-scale self-assembling delivery systems for cutaneous gene therapy. DNA/gemini surfactant (spacer n=3-16; chain m=12 or 16) complexes (1:10 charge ratio), with or without dioleoylphosphatidyl-ethanolamine (DOPE), designed for cellular transfection, were generally in the range of 100-200nm as demonstrated by atomic force microscopy and particle size analysis. Small-angle X-ray scattering measurements indicated that the DNA/gemini complexes lacked long-range order, whereas DNA/gemini/DOPE complexes exhibited lamellar and polymorphic phases other than hexagonal. Correlation studies using transfection efficiency data in PAM 212 keratinocytes and in vitro skin absorption indicated that formulations containing gemini surfactants having the ability to induce structures other than lamellar in the resulting complexes, generally exhibited greater transfection activity and cutaneous absorption.