Physicochemical properties of lipopeptide-based liposomes and their complexes with siRNA

Abstract

siRNA/cationic liposome complexes are efficient systems for transmembrane delivery. The aim of this study was to prepare a novel complex consisted of lipotripeptide OrnOrnGlu(C16H33)2 and siRNA molecule and examined their physicochemical properties. Electron microscopy study has shown that the siRNA/liposome complex (m/m 1/10) tends to form sandwich-like structures that may protect nucleic acid from nuclease degradation. Photon correlation spectroscopy data indicate that the particle size increased after siRNA adding, but did not exceed 300 nm in diameter, while z-potential of lipoplexes decreased from 22 mV to 14 mV, compared to the empty liposomes thus indicating positive charge neutralization by negatively charged siRNA. These data allow to hypothesize that such size and total positive charge could provide efficient cellular uptake by endocytosis. That may have good prospects for gene silencing therapy.

Diversity of PEGylation methods of liposomes and their influence on RNA delivery

“…Thus, cationic liposomes seem to be suitable vectors for siRNA delivery. [6][7][8] "Stealth" liposomes To obtain "stealth" or sterically stabilized liposomes, modification of the bilayer surface with inert polymers, which control semi-phase processes and prevent interaction of liposomes and blood components, exhibiting the so-called "stealth" properties is used. Improvement of the "stealth" properties of nanoparticles is the key goal of drug delivery, as the efficiency of drug delivery systems is closely related to their circulation time.…”

Transfection efficacy and drug release depends upon the PEG derivative in cationic lipoplexes: Evaluation in 3D in vitro model and in vivo

“…Two types of lipoplexes, namely pGL3–lipoplexes and siRNA‐lipoplexes, were obtained by mixing liposomes with pGL3 plasmid and siRNA, respectively. Appropriate N / P ratios of negatively charged nucleic acid phosphate groups/positively charged liposomal amine groups have been previously chosen by the gel retardation assay 7 . The obtained mixtures with N / P ratios of 32/1 and 64/1 were incubated at room temperature for 15 min.…”

“…Appropriate N/P ratios of negatively charged nucleic acid phosphate groups/positively charged liposomal amine groups have been previously chosen by the gel retardation assay. 7 The obtained mixtures with N/P ratios of 32/1 and 64/1 were incubated at room temperature for 15 min. Fluorescent labels Vic (λ ex/em 538/554 nm) and pyrene (λ ex/em 380/400 nm) were used for siRNA and liposomes visualization by confocal microscopy and in vivo experiments.…”

“…Among other commonly used synthetic nucleic acid carriers, cationic liposomes are known to provide rather high transfection efficiency. Thus, various cationic lipid–nucleic acid complexes for gene delivery and silencing have been described earlier 7 . A number of cationic lipids have been reported for development of DNA and RNA delivery systems used in vaccines, antiviral drugs, antitumor agents, and drugs for treatment of genetic disorders 8–10 …”

“…Thus, various cationic lipid-nucleic acid complexes for gene delivery and silencing have been described earlier. 7 A number of cationic lipids have been reported for development of DNA and RNA delivery systems used in vaccines, antiviral drugs, antitumor agents, and drugs for treatment of genetic disorders. [8][9][10] Classical liposomes, so-called liposomes of first generation, are widely employed for different biomedical applications.…”