TY - JOUR
T1 - Studies of the physicochemical and structural properties of self-assembling cationic pyridine derivatives as gene delivery agents
AU - Petrichenko, Oksana
AU - Rucins, Martins
AU - Vezane, Aleksandra
AU - Timofejeva, Irena
AU - Sobolev, Arkadij
AU - Cekavicus, Brigita
AU - Pajuste, Karlis
AU - Plotniece, Mara
AU - Gosteva, Marina
AU - Kozlovska, Tatjana
AU - Plotniece, Aiva
N1 - Funding Information:
The authors are thankful for the financial support from the European Regional Development Fund (ERDF) project No. 2DP/2.1.1.1.0/14/APIA/VIAA/060 , the Latvian National Research Programme BIOMEDICINE , and InnovaBalt (REGPOT-CT-2013-316149) project for O. Petrichenko as well as COST action CM1101 for fruitful discussion and possibility for dissemination of preliminary results. We are also grateful to Professor G. Duburs for initiation and support of development of these studies and to Dr. J. Kleperis of the Institute of Solid State Physics, University of Latvia for the use and assistance with the thermogravimetric measurements.
Publisher Copyright:
© 2015 Elsevier Ireland Ltd.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - New amphiphilic pyridine derivatives containing dodecyloxycarbonyl substituents at positions 3 and 5 and cationic moieties at positions 2 and 6 have been designed and synthesised. Compounds of this type can be considered as synthetic lipids. The corresponding 1,4-dihydropyridine (1,4-DHP) derivatives have earlier been proposed as a promising tool for plasmid DNA (pDNA) delivery in vitro. In this work studies of the self-assembling properties of amphiphilic pyridine derivatives leading to the formation of liposomes, determination of particle size, zeta-potential and critical micelle concentration (CMC) with dynamic light scattering (DLS) measurements are described. Furthermore, thermal analysis of pyridine derivatives was performed using thermogravimetry analysis (TGA) and differential thermal analysis (DTA) as well as the ability to deliver the pEGFP-C1 plasmid DNA (that encodes GFP reporter) into the Baby hamster kidney-derived (BHK-21) cell line was used for evaluation of gene delivery properties. We have revealed that the new pyridine derivatives possessed self-assembling properties which were proved by formation of nanoparticles with the average size from 115 to 743 nm, the zeta-potentials in the range of 48-79 mV and CMC values in the range of 2-67 μM. DTA data showed that all processes were endothermic for all compounds. Additionally, we established that among the tested pyridines the representatives with N-methylpyrrolidinium or pyridinium moieties as cationic head-group at the positions 2 and 6 possessed higher pEGFP-C1 transfection activity into the BHK-21 cell line. Nevertheless, the obtained results indicated that correlation of the physicochemical, structural properties and gene delivery activities of the tested compounds were not completely elucidated yet. On the other hand, the synthesised pyridines as possible metabolites of promising delivery systems on the 1,4-DHP core possessed lower pDNA transfection activity than the corresponding 1,4-DHP amphiphiles.
AB - New amphiphilic pyridine derivatives containing dodecyloxycarbonyl substituents at positions 3 and 5 and cationic moieties at positions 2 and 6 have been designed and synthesised. Compounds of this type can be considered as synthetic lipids. The corresponding 1,4-dihydropyridine (1,4-DHP) derivatives have earlier been proposed as a promising tool for plasmid DNA (pDNA) delivery in vitro. In this work studies of the self-assembling properties of amphiphilic pyridine derivatives leading to the formation of liposomes, determination of particle size, zeta-potential and critical micelle concentration (CMC) with dynamic light scattering (DLS) measurements are described. Furthermore, thermal analysis of pyridine derivatives was performed using thermogravimetry analysis (TGA) and differential thermal analysis (DTA) as well as the ability to deliver the pEGFP-C1 plasmid DNA (that encodes GFP reporter) into the Baby hamster kidney-derived (BHK-21) cell line was used for evaluation of gene delivery properties. We have revealed that the new pyridine derivatives possessed self-assembling properties which were proved by formation of nanoparticles with the average size from 115 to 743 nm, the zeta-potentials in the range of 48-79 mV and CMC values in the range of 2-67 μM. DTA data showed that all processes were endothermic for all compounds. Additionally, we established that among the tested pyridines the representatives with N-methylpyrrolidinium or pyridinium moieties as cationic head-group at the positions 2 and 6 possessed higher pEGFP-C1 transfection activity into the BHK-21 cell line. Nevertheless, the obtained results indicated that correlation of the physicochemical, structural properties and gene delivery activities of the tested compounds were not completely elucidated yet. On the other hand, the synthesised pyridines as possible metabolites of promising delivery systems on the 1,4-DHP core possessed lower pDNA transfection activity than the corresponding 1,4-DHP amphiphiles.
KW - DNA delivery
KW - Dynamic light scattering
KW - Liposomes
KW - Self-assembling pyridines
KW - Synthetic lipids
KW - Thermogravimetric analysis
UR - http://www.scopus.com/inward/record.url?scp=84939535661&partnerID=8YFLogxK
U2 - 10.1016/j.chemphyslip.2015.08.005
DO - 10.1016/j.chemphyslip.2015.08.005
M3 - Article
C2 - 26272034
AN - SCOPUS:84939535661
SN - 0009-3084
VL - 191
SP - 25
EP - 37
JO - Chemistry and Physics of Lipids
JF - Chemistry and Physics of Lipids
M1 - 4403
ER -