Insights into the Influences of Carboxymethyl-β-Cyclodextrin on DNA Formulations Characteristics and Gene Transfection Efficiency

Elsana, Hassan; Mysina, Svetlana; Elkordy, Eman Ali; Carr-Wilkinson, Jane; Elkordy, Amal

doi:10.2174/1567201815666180226115503

Cited by 4 publications

(4 citation statements)

References 21 publications

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“…DNA condensation is a prerequisite for successful gene delivery. Carboxymethyl-β-cyclodextrin has shown to be effective in gene delivery and our previous study 14 demonstrated that carboxymethyl-β-cyclodextrin has the ability to condense DNA at a molar ratio of 1:3 with 22% encapsulation efficiency. To investigate this further carboxymethyl-β-cyclodextrin (CD) was incorporated with cationic lipid (DOTAP), netural lipid (DOPE) and cholesterol to form liposomes to study the effect on gene cationic liposomes transfection and to evaluate the degree of gene encapsulation efficiency.…”

Section: Resultsmentioning

confidence: 91%

Evaluation of novel cationic gene based liposomes with cyclodextrin prepared by thin film hydration and microfluidic systems

Elsana

Olusanya

Carr-Wilkinson

et al. 2019

Sci Rep

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In gene delivery, non-viral vectors have become the preferred carrier system for DNA delivery. They can overcome major viral issues such as immunogenicity and mutagenicity. Cationic lipid-mediated gene transfer is one of the most commonly used non-viral vectors, which have been shown to be a safe and effective carrier. However, their use in gene delivery often exhibits low transfection efficiency and stability. The aim of this study was to examine the effectiveness of novel non-viral gene delivery systems. This study has investigated the encapsulation and transfection efficiency of cationic liposomes prepared from DOTAP and carboxymethyl-β-cyclodextrin (CD). The encapsulation efficiency of the CD-lipoplex complexes were also studied with and without the addition of Pluronic-F127, using both microfluidic and thin film hydration methods. In vitro transfection efficiencies of these complexes were determined in COS7 and SH-SY5Y cell lines. Formulation stability was evaluated using liposomes size, zeta potential and polydispersity index. In addition, the external morphology was studied using transmission electron microcopy (TEM). Results revealed that formulations produced by microfluidic method had smaller, more uniform and homogenious size and zeta-potential as well as higher encapsulation efficiency when compared with liposomes manufactured by thin film hydration method. Overall, the results of this study show that carboxymethyl-β-cyclodextrin increased lipoplexes’ encapsulation efficiency using both NanoAssemblr and rotary evaporator manufacturing processes. However, this increase was reduced slightly following the addition of Pluronic-F127. The addition of carboxymethyl-β-cyclodextrin to cationic liposomes resulted in an increase in transfection efficiency in mammalian cell lines. However, this increase appeared to be cell line specific, COS7 showed higher transfection efficiency compared to SH-SY5Y.

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Section: Resultsmentioning

confidence: 91%

Evaluation of novel cationic gene based liposomes with cyclodextrin prepared by thin film hydration and microfluidic systems

Elsana

Olusanya

Carr-Wilkinson

et al. 2019

Sci Rep

Self Cite

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“…] is a common redox indicator that is frequently used for the characterization of the DNA sensor assembling [25,33,34]. Moreover, it is a part of redox pair applied in the faradaic EIS technique for assessment of the conditions of electron exchange on the modified electrodes including electrochemical biosensors.…”

Section: Ferricyanide Ionmentioning

confidence: 99%

“…Thus, complexation of daunorubicin with β-cyclodextrin accelerated the intercalation of DNA [24]. Formulations with DNA and carboxymethyl-β-cyclodextrin showed high stability, indicating high incorporation of DNA within the macrocycle [25]. Pillar [5]arene derivatives were tested in DNA compactization [26] and assembling of nanocontainers in gene therapy [27].…”

Section: Introductionmentioning

confidence: 99%

Electrochemical Sensing of Interactions between DNA and Charged Macrocycles

et al. 2021

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In this work, we investigated aggregation of native DNA and thiacalix[4]arene derivative bearing eight terminal amino groups in cone configuration using various redox probes on the glassy carbon electrode. It was shown that sorption transfer of the aggregates on the surface of the electrode covered with carbon black resulted in changes in electrostatic interactions and diffusional permeability of the surface layer. Such changes alter the signals of ferricyanide ion, methylene green and hydroquinone as redox probes to a degree depending on their specific interactions with DNA and own charge. Inclusion of DNA in the surface layer was independently confirmed by scanning electron microscopy, electrochemical impedance spectroscopy and experiments with doxorubicin as a model intercalator. Thermal denaturing of DNA affected the charge separation on the electrode interface and the signals of redox probes. Using hydroquinone, less sensitive to electrostatic interactions, made it possible to determine from 10 pM to 1.0 nM doxorubicin (limit of detection 3 pM) after 10 min incubation. Stabilizers present in the commercial medications did not alter the signal. The DNA sensors developed can find future application in the assessment of the complexes formed by DNA and macrocycles as delivery agents for small chemical species.

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“…However, systems have been successfully engineered which allow for DNA condensation within the CD pocket [109]. Gene delivery can be achieved through the usage of carboxymethyl-β-cyclodextrin, a simple modification which is commercially available [110]. Some groups have had success delivering DNAzymes, which form 1:1 polyplexes with CD and can target and suppress genes of interest [107,111].…”

Section: Pure CD Vectorsmentioning

confidence: 99%

Cyclodextrins in drug delivery: applications in gene and combination therapy

Haley

Gottardi

Langer

et al. 2020

Drug Deliv. and Transl. Res.

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Gene therapy is a powerful tool against genetic disorders and cancer, targeting the source of the disease rather than just treating the symptoms. While much of the initial success of gene delivery relied on viral vectors, non-viral vectors are emerging as promising gene delivery systems for efficacious treatment with decreased toxicity concerns. However, the delivery of genetic material is still challenging, and there is a need for vectors which show improved targeting, further reduced toxicity, and controlled release. In this article, we highlight current work in gene therapy which utilizes the cyclic oligosaccharide molecule cyclodextrin (CD). With a number of unique abilities, such as hosting small molecule drugs, acting as a linker or modular component, reducing immunogenicity, and disrupting membranes, CD is a valuable constituent in many delivery systems. Further, it shows great promise in combination therapies due to the ease of assembling macromolecular structures and wide variety of chemical derivatives, which allow for customizable delivery systems and simultaneous co-delivery of therapeutics. The use of combination and personalized therapies can result in improved patient health -modular systems, such as those which incorporate CD, are more conducive to these therapy types.

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Insights into the Influences of Carboxymethyl-β-Cyclodextrin on DNA Formulations Characteristics and Gene Transfection Efficiency

Abstract: pDNA/CM-β-CD complex has not only shown to be able to transfect COS 7 and SHSY5Y cell lines, but it gives a higher transfection efficiency than that produced by the TransIT-LT1 commercial transfection reagent.

Cited by 4 publications

References 21 publications

Evaluation of novel cationic gene based liposomes with cyclodextrin prepared by thin film hydration and microfluidic systems

Evaluation of novel cationic gene based liposomes with cyclodextrin prepared by thin film hydration and microfluidic systems

Electrochemical Sensing of Interactions between DNA and Charged Macrocycles

Cyclodextrins in drug delivery: applications in gene and combination therapy

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