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STRUCTURAL ANALYSIS OF SELECTED GEMINI SURFACTANT (1-IMIDAZOLILO-3-DECYLOOXYMETHYL) PENTANE

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ISSRNS 2012: Abstracts / Synchrotron Radiation in Natural Science Vol. 11, No 1 – 2 (2012) P 51

STRUCTURAL ANALYSIS OF SELECTED GEMINI SURFACTANT (1-IMIDAZOLILO-3-DECYLOOXYMETHYL) PENTANE

CHLORIDE LIPOPLEXES

Z. Pietralik, R. Krzyszto´n, and M. Kozak

1Department of Macromolecular Physics, Faculty of Physics, Adam Mickiewicz University, Umultowska 85, 61-614 Pozna´n, Poland

Keywords: gemini surfactants, phospholipids, DSC, FTIR

e-mail : mkozak@amu.edu.pl

Cationic amphiphilic agents are one of the well established components for non-viral gene delivery vectors for gene therapy [1, 2]. Their natural ability to form self-assembled structures together with nu- cleic acids in water provides a protection of genetic material in vivo environment. Moreover, their posi- tively charged hydrophilic parts demonstrate a great affinity to polyanionic nucleic acids, reducing strong repulsive interaction with cell membranes and caus- ing significant condensation of attracted molecules.

Those properties have a response in increased cell internalisation of nucleic acids and enhanced trans- fection [2].

A new class of amphiphilic cationic surfac- tants — gemini surfactants [3], is currently stud- ied for gene delivery purposes [4, 5]. The gem- ini surfactant molecule is composed of two hy- drophilic “head” groups attached to hydrophilic

“tail” chains and connected via the molecular linker between them. The mixtures of cationic surfac- tants and lipids are recently under investigation [5, 6]. In our study mixtures of phosphatidylho- line derivatives (e.g. 1,2-dipalmitoyl-sn-glycero-3- phosphocholine [DPPC], 1,2-dimyristoyl-sn-glycero- 3-phosphocholine [DMPC]) and gemini surfactants with cationic imidazole “head” groups are tested.

The influence of different concentrations of 1,5-bis (1-imidazolilo-3-decylooxymethyl) pentane chloride (cationic gemini surfactant) on the ther- motropic phase behaviour of 1,2-dimyristoyl-sn- glycero-3-phosphocholine (DMPC) (PC derivative) bilayers was investigated using FTIR spectroscopy and differential scanning calorimetry DSC.

FTIR spectra were obtained by using BRUKER TENSOR 27 FT-IR spectrometer. DSC measure- ments were performed using DSC-204 Phoenix Net- zsch system with a high sensitivity µ-sensor.

Thermotropic transitions between gel (Lβ) → rippled gel (Pβ) and rippled gel (Pβ) → liquid

crystalline (Lα) phases were observed. FTIR anal- ysis of CH2l, CH3 symmetric and antisymmetric stretching, as well as CH2 scissoring bands showed discontinuous conformational changes in DMPC hy- drophobic chains. Hydration of DMPC hydrophilic heads was investigated by analysis of C = O stretch- ing band. DSC analysis showed a decrease in en- thalpy (∆H) of the main transition (Pβ → Lα) in correlation with the increase in (1-imidazolilo-3- decylooxymethyl) pentane chloride concentration.

Acknowledgments: The research was supported by research grant (UMO-2011/01/B/ST5/00846) from Na- tional Science Centre (Poland).

References

[1] D. Deshpande, P. Blezinger, R. Pillai, J. Duguid, B.

Freimark, A. Rolland, “Target specific optimization of cationic lipid-based systems for pulmonary gene therapy,” Pharm. Res. 15 (1998) 1340 – 1347.

[2] W. Li , F.C. Szoka Jr., “Lipid-based nanoparti- cles for nucleic acid delivery,” Pharm. Res. 3 (2007) 438 – 449.

[3] S.K. Hait, S.P. Moulik, “Gemini surfactants: A dis- tinct class of self-assembling molecules,” Curr. Sci.

82 (2002) 1101 – 1111.

[4] A.J Kirby et al., “Gemini surfactants: New synthetic vectors for gene transfection,” Angew. Chem. Int.

Ed. Engl. 42 (2003) 1448 – 1457.

[5] C. Bomelli, F. Faggioli, P. Luciani, G. Mancini, M.G. Sacco, “Efficient transfection of DNA by liposomes formulated with cationic gemini am- phiphiles,” J. Med. Chem. 48 (2005) 5378 – 5382.

[6] J.A.S. Almeida et al., “Structure and order of DODAB bilayers modulated by dicationic gemini surfactants,” Phys. Chem. Chem. Phys. 13 (2011) 13772 – 13782.

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