Rationally Designed Synthetic Vectors for Gene Delivery

Rao, Gururaj; Yadava, Preeti; Hughes, Jeffrey A.

doi:10.2174/1874126600701010007

Cited by 8 publications

(1 citation statement)

References 139 publications

(111 reference statements)

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“…Было установлено, что КЛ с одной углеводородной цепью проявляют большую токсичность и обладают более низкой ЭТ по сравнению с КЛ с двумя цепями [46]. Однако было показано, что соединение 6, содержащее один остаток додекановой кислоты в качестве ГД, оказалось не только более эффективным, но и менее токсичным, чем DOTAP (2) [47]. Учитывая различную зависимость ЭТ от токсичности КЛ, а также строения их гидрофобного домена, последний должен подбираться отдельно.…”

Section: катионные липидыunclassified

Сationic liposomes as delivery systems for nucleic acids

et al. 2020

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Objectives. Gene therapy is based on the introduction of genetic material into cells, tissues, or organs for the treatment of hereditary or acquired diseases. A key factor in the success of gene therapy is the development of delivery systems that can efficiently transfer genetic material to the place of their therapeutic action without causing any associated side effects. Over the past 10 years, significant effort has been directed toward creating more efficient and biocompatible vectors capable of transferring nucleic acids (NAs) into cells without inducing an immune response. Cationic liposomes are among the most versatile tools for delivering NAs into cells; however, the use of liposomes for gene therapy is limited by their low specificity. This is due to the presence of various biological barriers to the complex of liposomes with NA, including instability in biological fluids, interaction with serum proteins, plasma and nuclear membranes, and endosomal degradation. This review summarizes the results of research in recent years on the development of cationic liposomes that are effective in vitro and in vivo. Particular attention is paid to the individual structural elements of cationic liposomes that determine the transfection efficiency and cytotoxicity. The purpose of this review was to provide a theoretical justification of the most promising choice of cationic liposomes for the delivery of NAs into eukaryotic cells and study the effect of the composition of cationic lipids (CLs) on the transfection efficiency in vitro.Results. As a result of the analysis of the related literature, it can be argued that one of the most promising delivery systems of NAs is CL based on cholesterol and spermine with the addition of a helper lipid DOPE. In addition, it was found that varying the composition of cationic liposomes, the ratio of CL to NA, or the size and zeta potential of liposomes has a significant effect on the transfection efficiency.Conclusions. Further studies in this direction should include optimization of the conditions for obtaining cationic liposomes, taking into account the physicochemical properties and established laws. It is necessary to identify mechanisms that increase the efficiency of NA delivery in vitro by searching for optimal structures of cationic liposomes, determining the ratio of lipoplex components, and studying the delivery efficiency and properties of multicomponent liposomes.

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Section: катионные липидыunclassified

Сationic liposomes as delivery systems for nucleic acids

et al. 2020

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DNA gel particles: An overview

Morán

Vinardell

Infante

et al. 2014

Advances in Colloid and Interface Science

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A general understanding of interactions between DNA and oppositely charged compounds forms the basis for developing novel DNA-based materials, including gel particles. The association strength, which is altered by varying the chemical structure of the cationic cosolute, determines the spatial homogeneity of the gelation process, creating DNA reservoir devices and DNA matrix devices that can be designed to release either single-(ssDNA) or double-stranded (dsDNA). This review covers recent developments on the topic of DNA gel particles formed in water-water emulsion-type interfaces. The degree of DNA entrapment, particle morphology, swelling/dissolution behaviour and DNA release responses are discussed as a function of the nature of the cationic agent used. On the basis of designing DNA gel particles for therapeutic purposes, recent studies on the determination of the surface hydrophobicity, the haemolytic and the cytotoxic assessments of the obtained DNA gel particles have been also reported.

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Gelatin-based nanoparticles as DNA delivery systems: Synthesis, physicochemical and biocompatible characterization

Morán

Rosell

Ruano

et al. 2015

Colloids and Surfaces B: Biointerfaces

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The rapidly rising demand for therapeutic grade DNA molecules requires associated improvements in encapsulation and delivery technologies. One of the challenges for the efficient intracellular delivery of therapeutic biomolecules after their cell internalization by endocytosis is to manipulate the non-productive trafficking from endosomes to lysosomes, where degradation may occur. The combination of the endosomal acidity with the endosomolytic capability of the nanocarrier can increase the intracellular delivery of many drugs, genes and proteins, which, therefore, might enhance their therapeutic efficacy. Among the suitable compounds, the gelification properties of gelatin as well as the strong dependence of gelatin ionization with pH makes this compound an interesting candidate to be used to the effective intracellular delivery of active biomacromolecules. In the present work, gelatin (either high or low gel strength) and protamine sulfate has been selected to form particles by interaction of oppositely charged compounds. Particles in the absence of DNA (binary system) and in the presence of DNA (ternary system) have been prepared. The physicochemical characterization (particle size, polydispersity index and degree of DNA entrapment) have been evaluated. Cytotoxicity experiments have shown that the isolated systems and the resulting gelatin-based nanoparticles are essentially non-toxic. The pH-dependent hemolysis assay and the response of the nanoparticles co-incubated in buffers at defined pHs that mimic extracellular, early endosomal and late endo-lysosomal environments demonstrated that the nanoparticles tend to destabilize and DNA can be successfully released. It was found that, in addition to the imposed compositions, the gel strength of gelatin is a controlling parameter of the final properties of these nanoparticles. The results indicate that these gelatin-based nanoparticles have excellent properties as highly potent and non-toxic intracellular delivery systems, rendering them promising DNA vehicles to be used as non-viral gene delivery systems.

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Rationally Designed Synthetic Vectors for Gene Delivery

Cited by 8 publications

References 139 publications

Сationic liposomes as delivery systems for nucleic acids

Сationic liposomes as delivery systems for nucleic acids

DNA gel particles: An overview

Gelatin-based nanoparticles as DNA delivery systems: Synthesis, physicochemical and biocompatible characterization

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