Spacer structure and hydrophobicity influences transfection activity of novel polycationic gemini amphiphiles

Some quaternary gemini amphiphiles (GAs) were synthesized as nonviral gene delivery carriers. The critical miceller concentration values of these amphiphiles are indicative of their superior surface-active properties. All of the synthesized GAs, alone or along with lipids like cholesterol and/or dioleoylphosphatidyl ethanolamine (DOPE), were formulated as liposomes. Formulations of GAs with DOPE showed average particle diameters of 326–400 nm with positive ζ-potential (30.1–46.4 mV). The lipoplexes of theses formulations showed complete pDNA retention at the base at a N/P ratio higher than 1.0 in gel retardation study. The GAs were effective in condensing pDNA into a ψ-phase, as indicated by circular dichroism study, and provided complete protection of the pDNA against the enzyme DNase at a N/P ratio more than 1. In vitro cell line studies showed that GA liposomal formulations caused β-gal expression and offered a higher transfection efficiency than that of liposomes prepared with the help of N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl-sulfate (DOTAP)/DOPE and dicyclocarbodiimide (DCC)/DOPE but comparable to those of Lipofectamine 2000 in A549 and HeLa cell lines. Modulation of head group polarity significantly affected the transfection efficacy of GAs. The cell viabilities of almost all of the formulations were comparable to those of the standards (DCC/DOPE and DOTAP/DOPE liposomes). Incorporation of cholesterol [GA/DOPE/cholesterol in the ratio of 1:1:1] further improved the serum compatibility of the formulations and improved the transfection efficacy when evaluated in A549 and HeLa cell lines. Fluorescence-assisted cell sorting studies showed comparable number of transfected cells to Lipofectamine 2000 in the HeLa cell line. Intracellular trafficking studies using confocal microscopy indicated transfection of the HeLa cells with the reporter gene within 30 min of lipoplex treatment. γ-Scintigraphy using 99mTc-labeled lipoplexes showed higher concentrations of the lipoplexes in vital tissues like liver, spleen, lungs, and kidneys.

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“…and lipophilic carriers such as quaternary ammonium lipids, lipoamines, and amidinium lipids are utilized for gene delivery applications. 8 − 12 …”

Section: Introductionmentioning

confidence: 99%

Gemini Amphiphile-Based Lipoplexes for Efficient Gene Delivery: Synthesis, Formulation Development, Characterization, Gene Transfection, and Biodistribution Studies

et al. 2018

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“…mean fluorescence intensity, and for 48c (N/P 8) in GFP silencing in BHK IR-780 cells. 158 At N/P < 4 the cyclen-based gemini surfactants 49-50 159 (Chart 9) were less toxic than Lipofectamine 2000™ in Chart 8 Carbohydrate classical and gemini transfectants.…”

Section: Geminis With Multivalent Head Groupsmentioning

confidence: 98%

Transfection by cationic gemini lipids and surfactants

Damen¹,

Groenen²,

Dongen³

et al. 2018

Med. Chem. Commun.

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“…Analogs 10e – g with ethoxypropylene, octamethylene, and ethoxyethoxyethylene spacers ( Figure 6 ) permitted a greater TA increase than using 10c in vitro [ 50 ]. In contrast, the replacement of spermine with triethylenetetramine (TETA, 11a , b ) led to a significant decrease in TA [ 51 ].…”

Section: Cationic Amphiphiles Based On Polyamines or Amino Acidsmentioning

confidence: 99%

“…Multiple studies have proven that a close arrangement of the hydrophobic and cationic domains complicates both domain’s functioning and interferes with the formation of liposomes. The introduction of a spacer into the CA structure and an increase in its length increase NA delivery efficiency [ 42 , 50 , 88 , 89 , 91 ].…”

Section: Cationic Amphiphiles Based On Polyamines or Amino Acidsmentioning

confidence: 99%

Lipophilic Polyamines as Promising Components of Liposomal Gene Delivery Systems

Puchkov

Маслов

2021

Pharmaceutics

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Gene therapy requires an effective and safe delivery vehicle for nucleic acids. In the case of non-viral vehicles, including cationic liposomes, the structure of compounds composing them determines the efficiency a lot. Currently, cationic amphiphiles are the most frequently used compounds in liposomal formulations. In their structure, which is a combination of hydrophobic and cationic domains and includes spacer groups, each component contributes to the resulting delivery efficiency. This review focuses on polycationic and disulfide amphiphiles as prospective cationic amphiphiles for gene therapy and includes a discussion of the mutual influence of structural components.

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Spacer structure and hydrophobicity influences transfection activity of novel polycationic gemini amphiphiles

Cited by 14 publications

References 29 publications

Gemini Amphiphile-Based Lipoplexes for Efficient Gene Delivery: Synthesis, Formulation Development, Characterization, Gene Transfection, and Biodistribution Studies

Gemini Amphiphile-Based Lipoplexes for Efficient Gene Delivery: Synthesis, Formulation Development, Characterization, Gene Transfection, and Biodistribution Studies

Transfection by cationic gemini lipids and surfactants

Lipophilic Polyamines as Promising Components of Liposomal Gene Delivery Systems

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