ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

pH-sensitive N,N-(dimethyl)-N-alkanamine-N-oxides as gene delivery vectors

Gilda Liskayová, Lukáš Hubčík, Katarína Šišková, Ingrid Pauliková, Dominika Galliková, Ferdinand Devínsky, Sergio S. Funari, and Daniela Uhríková

Department of Physical Chemistry of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia

E-mail: liskayova@fpharm.uniba.sk

Abstract: N,N-(Dimethyl)-N-alkanamine-N-oxides C_nNO (n = 12 and 16) are amphiphiles that exist in neutral as well as in cationic forms depending on pH of aqueous solutions. C_nNO with a neutral lipid DOPE (dioleoylphosphatidylethanolamine) can form liposomes with positive surface charge in acidic pH solution. C_nNO/DOPE (n = 12 and 16) liposomes were used for preparation of DNA delivery vectors. Small-angle X-ray diffraction (SAXD) was used to determine the structure of C_nNO/DOPE/DNA complexes prepared at various pH and 20 °C. At acidic pH, we observe a condensed lamellar phase L^C with DNA strands packed regularly. With increasing pH, a coexistence of two lamellar phases is recognized. The amount of DNA bound into C_nNO/DOPE/DNA complexes shows significant dependence on pH as derived from UV/Vis spectroscopy. Up to ~99% of total DNA was complexed at acidic pH. The cytotoxicity of C₁₂NO/DOPE for HepG2 cells at acidic pH is low as determined by Janus Green Staining Assay.

Keywords: DNA; N,N-(Dimethyl)-N-alkanamine-N-oxides; Dioleoylphosphatidylethanolamine; UV/Vis spectroscopy; X-ray structure determination

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-017-0171-2

Chemical Papers 71 (9) 1739–1748 (2017)