Contribution of Molecular Structure to Self-Assembling and Biological Properties of Bifunctional Lipid-Like 4-(N-Alkylpyridinium)-1,4-Dihydropyridines

6533b81ffe1ef96bd1277d46

RESEARCH PRODUCT

Contribution of Molecular Structure to Self-Assembling and Biological Properties of Bifunctional Lipid-Like 4-(N-Alkylpyridinium)-1,4-Dihydropyridines

Janis Liepins Pavels Dimitrijevs Mara Plotniece Dace Tirzite Signe Kibilda Anita Gulbe Ilona Domracheva Arkadij Sobolev Oksana Petrichenko Ludmila Jackevica Karlis Pajuste Klavs Pajuste Martins Rucins Aiva Plotniece Krisjanis Smits

subject

Cytotoxicity DLS toxicity on microorganisms Pharmaceutical Science Nanoparticle lcsh:RS1-441 02 engineering and technology Synthetic lipids 010402 general chemistry 01 natural sciences Hydrophobic effect Toxicity on microorganisms lcsh:Pharmacy and materia medica self-assembling properties chemistry.chemical_compound Phospholipid binding Amphiphile Polymer chemistry synthetic lipids :NATURAL SCIENCES:Physics [Research Subject Categories]pyridinium and propargyl moieties Moiety Bifunctional Alkyl Self-assembling properties chemistry.chemical_classification 021001 nanoscience & nanotechnology 3. Good health 0104 chemical sciences phospholipid binding chemistry Propargyl TEM Nanoparticles cytotoxicity nanoparticles Pyridinium 0210 nano-technology Pyridinium and propargyl moieties

description

The design of nanoparticle delivery materials possessing biological activities is an attractive strategy for the development of various therapies. In this study, 11 cationic amphiphilic 4-(N-alkylpyridinium)-1,4-dihydropyridine (1,4-DHP) derivatives differing in alkyl chain length and propargyl moiety/ties number and position were selected for the study of their self-assembling properties, evaluation of their cytotoxicity in vitro and toxicity on microorganisms, and the characterisation of their interaction with phospholipids. These lipid-like 1,4-DHPs have been earlier proposed as promising nanocarriers for DNA delivery. We have revealed that the mean diameter of freshly prepared nanoparticles varied from 58 to 513 nm, depending upon the 4-(N-alkylpyridinium)-1,4-DHP structure. Additionally, we have confirmed that only nanoparticles formed by 4-(N-dodecylpyridinium)-1,4-DHP derivatives 3 and 6, and by 4-(N-hexadecylpyridinium)-1,4-DHP derivatives 10 and 11 were stable after two weeks of storage. The nanoparticles of these compounds were found to be homogenous in size distribution, ranging from 124 to 221 nm. The polydispersity index (PDI) values of 1,4-DHPs samples 3, 6, 10, and 11 were in the range of 0.10 to 0.37. We also demonstrated that the nanoparticles formed by 4-(N-dodecylpyridinium)-1,4-DHP derivatives 3, 6, and 9, and 4-(N-hexadecylpyridinium)-1,4-DHP derivatives 10 and 11 had zeta-potentials from +26.07 mV (compound 6) to +62.80 mV (compound 11), indicating a strongly positive surface charge and confirming the relative electrostatic stability of these nanoparticle solutions. Transmission electron microscopy (TEM) images of nanoaggregates formed by 1,4-DHPs 3 and 11 confirmed liposome-like structures with diameters around 70 to 170 nm. The critical aggregation concentration (CAC) value interval for 4-(N-alkylpyridinium)-1,4-DHP was from 7.6 &micro

year	journal	country	edition	language
2019-03-12	Pharmaceutics

10.3390/pharmaceutics11030115 http://dx.doi.org/10.3390/pharmaceutics11030115