Parameters affecting organization and transfection efficiency of amphiphilic copolymers/DNA carriers

Roques, Caroline; Bouchemal, Kawthar; Ponchel, Gilles; Fromes, Yves; Fattal, Elias

doi:10.1016/j.jconrel.2009.04.030

Cited by 35 publications

(44 citation statements)

References 27 publications

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“…The transfection mechanism of Pluronics is not yet completely understood (Netticadan et al, 2000;Yang et al, 2008), but the fact that they do not condense DNA, and their flexibility and efficiency in releasing plasmid DNA, might explain their wide range of transfection (Kabanov et al, 2005;Roques et al, 2009b). Pluronics have been shown to be safe and repeatable synthetic formulations to deliver nucleic acids without adverse immune reactions (Sriadibhatla et al, 2006;Roques et al, 2009a). Furthermore, we did not detect transgene dissemination in the liver, lungs, and kidneys.…”

Section: Discussionmentioning

confidence: 70%

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SERCA2a Gene Therapy Can Improve Symptomatic Heart Failure in δ-Sarcoglycan-Deficient Animals

2014

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The loss of dystrophin or its associated proteins results in the development of muscle wasting frequently associated with cardiomyopathy. Contractile cardiac tissue is injured and replaced by fibrous tissue or fatty infiltrates, leading to a progressive decrease of the contractile force and finally to end-stage heart failure. At the time symptoms appear, restoration of a functional allele of the causative gene might not be sufficient to prevent disease progression. Alterations in Ca 2 + transport and intracellular calcium levels have been implicated in many types of pathological processes, especially in heart disease. On the basis of a gene transfer strategy, we analyzed the therapeutic efficacy of primary gene correction in a d-sarcoglycan (d-SG)-deficient animal model versus gene transfer of the Ca 2 + pump hSERCA2a (human sarco-endoplasmic reticulum calcium ATPase 2a), at a symptomatic stage of heart disease. Our results strongly suggest that restoration of d-SG at this stage of disease will not lead to improved clinical outcome. However, restoration of proper Ca 2 + handling by means of amplifying SERCA2a expression in the myocardium can lead to functional improvement. Abnormalities in Ca 2 + handling play an important role in disease progression toward heart failure, and increased SERCA2a levels appear to significantly improve cardiac contraction and relaxation. Beneficial effects persist at least over a period of 6 months, and the evolution of cardiac functional parameters paralleled those of normal controls. Furthermore, we demonstrate that a plasmid formulation based on amphiphilic block copolymers can provide a safe and efficient platform for myocardial gene therapies. The use of synthetic formulations for myocardial gene transfer might thus overcome one of the major hurdles linked to viral vectors, that is, repeat administrations.

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Section: Discussionmentioning

confidence: 70%

“…On the basis of former work, we used a Pluronic block copolymer formulation. Some studies showed their efficacy in cardiac and skeletal muscle gene transfer and an optimized formulation for dystrophic muscle (Kabanov et al, 2002;Roques et al, 2009a).…”

Section: Introductionmentioning

confidence: 99%

SERCA2a Gene Therapy Can Improve Symptomatic Heart Failure in δ-Sarcoglycan-Deficient Animals

2014

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“…Under this experimental condition, thermodynamic reactions derived from the phase of (ii) and (iii) may be observed. The non-sigmoidal thermograms were analyzed according to a method that has been reported by many authors 23,29,30) and enables a rough estimation to be made of the start of transition (ST) and end of transition (ET) corresponding to the start and end of the micellization process. As shown in Fig.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of the Micellization Mechanism of an Amphipathic Graft Copolymer with Enhanced Solubility of Ipriflavone

et al. 2016

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The main purpose of this study was to investigate the solubilization enhancement properties of an amphipathic graft copolymer, Soluplus ® , on test compounds. Micellization of Soluplus ® in solution was characterized by evaluating the changes in the surface activity, turbidity, and thermodynamic behavior. To assess the feasibility of Soluplus ® as a polymeric carrier of solid dispersions, freeze-dried samples of ipriflavone were prepared, and the physicochemical properties of the carrier plus ipriflavone were evaluated in terms of solubility, dissolution, and crystallinity. The surface tension of the solution decreased depending on the polymer concentration, and gradual turbidity increase was observed. Isothermal titration calorimetry was used to measure the thermal reaction accompanying the micellization of Soluplus ® and indicated that a colloidal micelle formation improved solubility. The prepared formulations, particularly at a ratio of ipriflavone : Soluplus ® 1 : 10 (w/w) exhibited a dramatically improved solubility of ipriflavone that was ca. 70-fold higher than that of untreated ipriflavone. The solubilization mechanism of Soluplus ® was partially elucidated and suggested that its strategic application could improve the solubility of hydrophobic compounds.Key words isothermal titration calorimetry; ipriflavone; amphipathic graft copolymer; solubility Among the available technologies, the solid dispersion technique is commonly used as one of the most promising strategies for the enhancement of the solubility, dissolution rate, and bioavailability of poorly water-soluble compounds. A solid dispersion system can be defined as a distribution of active pharmaceutical ingredients as molecular amorphous particles and/or in the microcrystalline state into a carrier matrix-like polymer.1) The physicochemical characteristics of polymeric carriers could dominate the pharmaceutical properties of a solid dispersion system. 2,3) Based on the characteristic properties of a polymeric carrier, a number of solid dispersion systems possessing various functional properties such as sustained release, pH-dependent release, self-emulsifying properties, and site-specific release have been developed. [4][5][6][7] In particular, amphiphilic polymers have been found to be beneficial for the enhancement of not only solubility but also of the oral bioavailability of poorly water-soluble compounds because they form micellar structures that contain the compound. 6,8) Soluplus ® , a graft copolymer consisting of polyvinyl caprolactam, polyvinyl acetate, and polyethyleneglycol, has been applied to the design of solid-dispersion formulations with poorly water-soluble substances to improve their solubility and bioavailability.9,10) The copolymer exhibits an amphipathic property attributed to its hydrophilic and hydrophobic residues, which could contribute to the formation of micelles in water. Unlike conventional polymers such as polyvinylpyrrolidone and hydroxypropyl methylcellulose, Soluplus ® is bifunctional and can act as both a polym...

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“…Four days after HLI surgery was performed, mice were randomly assigned to receive 200 µg pIRES-EGFP or 200 µg pIRESNDhh together with 0.05% pluronic, as described previously. 27 The DNA/pluronic mix was injected intramuscularly in the tibialis anterior muscle. Mice were euthanized 10 days after HLI surgery was performed.…”

Section: Plasmids/gene Therapymentioning

confidence: 99%

Desert Hedgehog Promotes Ischemia-Induced Angiogenesis by Ensuring Peripheral Nerve Survival

Renault

Chapouly

Yao

et al. 2013

Circulation Research

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Rationale: Blood vessel growth and patterning have been shown to be regulated by nerve-derived signals. Desert hedgehog (Dhh), one of the Hedgehog family members, is expressed by Schwann cells of peripheral nerves. Objective: The purpose of this study was to investigate the contribution of Dhh to angiogenesis in the setting of ischemia. Methods and Results: We induced hindlimb ischemia in wild-type and Dhh –/– mice. First, we found that limb perfusion is significantly impaired in the absence of Dhh. This effect is associated with a significant decrease in capillary and artery density in Dhh –/– . By using mice in which the Hedgehog signaling pathway effector Smoothened was specifically invalidated in endothelial cells, we demonstrated that Dhh does not promote angiogenesis by a direct activation of endothelial cells. On the contrary, we found that Dhh promotes peripheral nerve survival in the ischemic muscle and, by doing so, maintains the pool of nerve-derived proangiogenic factors. Consistently, we found that denervation of the leg, immediately after the onset of ischemia, severely impairs ischemia-induced angiogenesis and decreases expression of vascular endothelial growth factor A, angiopoietin 1, and neurotrophin 3 in the ischemic muscle. Conclusions: This study demonstrates the crucial roles of nerves and factors regulating nerve physiology in the setting of ischemia-induced angiogenesis.

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Parameters affecting organization and transfection efficiency of amphiphilic copolymers/DNA carriers

Cited by 35 publications

References 27 publications

SERCA2a Gene Therapy Can Improve Symptomatic Heart Failure in δ-Sarcoglycan-Deficient Animals

SERCA2a Gene Therapy Can Improve Symptomatic Heart Failure in δ-Sarcoglycan-Deficient Animals

Evaluation of the Micellization Mechanism of an Amphipathic Graft Copolymer with Enhanced Solubility of Ipriflavone

Desert Hedgehog Promotes Ischemia-Induced Angiogenesis by Ensuring Peripheral Nerve Survival

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