<i>In vivo</i> cutaneous interferon‐γ gene delivery using novel dicationic (gemini) surfactant–plasmid complexes

Badea, Ildikó; Verrall, R. E.; Baca-Estrada, Maria E.; Tikoo, Suresh K.; Rosenberg, Alan; Kumar, Praveen; Földvári, Marianna

doi:10.1002/jgm.763

Cited by 113 publications

(158 citation statements)

References 55 publications

(58 reference statements)

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“…In our preliminary study, 3-day TNP treatment produced similar IFN-g levels to those measured in the skin of CD1 animals treated topically for 3 days with the TNP formulation, 16 as well as by topical treatment of IFN-g-deficient mice 17 (results not shown). In the Tsk/ þ mice, after the 20-day treatment regimen, intradermal injections with plasmid solutions appeared to produce higher transgene expression (1069 ± 612 pg cm…”

Section: Resultssupporting

confidence: 54%

“…16 The topical cationic nanoparticles (TNP) were prepared with 1,2-dioleoyl-sn-glycero-phosphatidylethanolamine (DOPE; Avanti Polar Lipids, Alabaster, AL, USA), 25 mg g À1 , purified phosphatidylcholine from soybean lecithin 25 mg g À1 , and the 16-3-16 gemini surfactant 10 mg g À1 formulation, an in-house synthesized amino acid derivative (PDM 27) 10 mg g À1 , propylene glycol 70 mg g À1 and a-tocopherol as an antioxidant. The applied dose was 100 mg plasmid per 100 mg formulation per cm 2 skin area.…”

Section: Topical Formulationsmentioning

confidence: 99%

“…15 Littermates (pa/pa) of þ Pldn pa / þ Pldn pa genotype do not show signs of the disease. We have previously shown that gemini surfactant-based selfassembled DNA nanoparticles (topical nanoparticles (TNPs)) deliver IFN-g-coding plasmid into keratinocytes in vitro and into skin of normal (CD1) mice, 16 as well as in IFN-g-deficient knockout mice. 17 The level of IFN-g gene expression in vivo was similar in the two animal models and was indicative of pharmacologically relevant levels.…”

Section: Introductionmentioning

confidence: 99%

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Effect of topical interferon-γ gene therapy using gemini nanoparticles on pathophysiological markers of cutaneous scleroderma in Tsk/+ mice

et al. 2011

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Scleroderma is a chronic disorder manifested by excessive synthesis and deposition of collagen in skin and connective tissue, vascular abnormalities, and autoimmunity. Using microarray and real-time PCR data, we show that intradermally expressed interferon g (IFN-g), generated after intradermal injection of IFN-g-coding plasmid, and non-invasive topical nanoparticle (TNP) treatment with IFN-g-coding plasmid, decreased collagen synthesis (via the Jak/Stat 1 pathway), upregulated Th1 cytokine levels, and downregulated the profibrotic cytokine Transforming growth factor b and the Smad pathways in the Tsk/ þ (tight-skin scleroderma) mouse model. The TNP gene delivery system was constructed from gemini surfactant 16-3-16 and IFN-g-coding plasmid. Topical administration of IFN-g-coding plasmid in TNPs was effective in expressing IFN-g levels after a 20-day treatment regimen without increased TLR4, CCL2, CCL11 and CCR2 mRNA levels that were observed in injected animals, signs considered to be innate responses to injury. The more uniform transgene IFN-g expression caused significant (70 --72%) collagen reduction, as assessed by reverse transcription real-time PCR. These results demonstrate efficient in vivo transfection using a gemini surfactant-based TNP delivery system able to modulate excessive collagen synthesis in scleroderma-affected skin.

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Section: Resultssupporting

confidence: 54%

Section: Topical Formulationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of topical interferon-γ gene therapy using gemini nanoparticles on pathophysiological markers of cutaneous scleroderma in Tsk/+ mice

et al. 2011

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“…injection [8][9][10][11] gene gun, 12,13 magnetofection, 14 electroporation [15][16][17][18][19][20] and topical formulations. [21][22][23][24][25][26] However, only limited success with sustainable gene expression has been observed over wide areas of the skin. 11,[27][28][29] Although the mechanism of nucleic acid uptake in keratinocytes is poorly understood, it has been shown in other organ systems that high pressure facilitates delivery.…”

Section: Introductionmentioning

confidence: 99%

Increased interstitial pressure improves nucleic acid delivery to skin enabling a comparative analysis of constitutive promoters

González-González

Spitler

et al. 2010

Gene Ther

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Nucleic acid-based therapies hold great promise for treatment of skin disorders if delivery challenges can be overcome. To investigate one mechanism of nucleic acid delivery to keratinocytes, a fixed mass of expression plasmid was intradermally injected into mouse footpads in different volumes, and reporter expression was monitored by intravital imaging or skin sectioning. Reporter gene expression increased with higher delivery volumes, suggesting that pressure drives nucleic acid uptake into cells after intradermal injections similar to previously published studies for muscle and liver. For spatiotemporal analysis of reporter gene expression, a dual-axis confocal (DAC) fluorescence microscope was used for intravital imaging following intradermal injections. Individual keratinocytes expressing hMGFP were readily visualized in vivo and initially appeared to preferentially express in the stratum granulosum and subsequently migrate to the stratum corneum over time. Fluorescence microscopy of frozen skin sections confirmed the patterns observed by intravital imaging. Intravital imaging with the DAC microscope is a noninvasive method for probing spatiotemporal control of gene expression and should facilitate development and testing of new nucleic acid delivery technologies.

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“…The potential nonviral liposomal genetic delivery systems were obtained empirically by modulating phospholipid and surfactant structures (particularly dicationic quaternary ammonium surfactants -gemini surfactants) [19][20][21].…”

Section: Introductionmentioning

confidence: 99%

SAXS Study of Influence of Gemini Surfactant, 1,1'-(1,4-butanediyl)bis 3-cyclododecyloxymethylimidazolium di-chloride, on the Fully Hydrated DMPC

et al. 2010

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The study has been performed on model systems of biological membranes obtained on the basis of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and cationic gemini surfactant -derivative of 1,1 -(1,4--butane)bis 3-alkyloxymethylimidazolium chlorides with cyclic chains. The small angle X-ray scattering SAXS results implied a gradual disappearance (as a function of surfactant concentration) of the lamellar phase typical of DMPC and formation of unilamellar phase -probably a bicellar phase.

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In vivo cutaneous interferon‐γ gene delivery using novel dicationic (gemini) surfactant–plasmid complexes

Cited by 113 publications

References 55 publications

Effect of topical interferon-γ gene therapy using gemini nanoparticles on pathophysiological markers of cutaneous scleroderma in Tsk/+ mice

Effect of topical interferon-γ gene therapy using gemini nanoparticles on pathophysiological markers of cutaneous scleroderma in Tsk/+ mice

Increased interstitial pressure improves nucleic acid delivery to skin enabling a comparative analysis of constitutive promoters

SAXS Study of Influence of Gemini Surfactant, 1,1'-(1,4-butanediyl)bis 3-cyclododecyloxymethylimidazolium di-chloride, on the Fully Hydrated DMPC

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