Dextran–protamine–solid lipid nanoparticles as a non-viral vector for gene therapy: In vitro characterization and in vivo transfection after intravenous administration to mice

Delgado, Diego; Rodríguez-Gascón, Alicia; Pozo-Rodríguez, Ana del; Echevarrı́a, Enrique; Garibay, Aritz Pérez Ruiz de; Rodríguez, Juan Manuel; Solinís, Maria Ángelés

doi:10.1016/j.ijpharm.2011.12.052

Cited by 79 publications

(51 citation statements)

References 41 publications

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“…Nanoparticle, as a non-viral vector with biodegradability and controlled release ability, has been popularly used in gene transfer [17,26,27]. Due to their nano-size range, polymeric nanoparticles containing genes could overcome the absorption barrier of the cell membrane by penetrating inside the cell via endocytosis [28,29].…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle-mediated delivery of TGF-β1 miRNA plasmid for preventing flexor tendon adhesion formation

et al. 2013

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Section: Introductionmentioning

confidence: 99%

Nanoparticle-mediated delivery of TGF-β1 miRNA plasmid for preventing flexor tendon adhesion formation

et al. 2013

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“…Exposure to solid lipid nanoparticles or PA-SLN at the range of concentrations previously used in vivo 37,38 resulted in decreased viability of HUVECs, which was not mediated by apoptosis, and increased production of nitric oxide only at the highest doses. Further, excessive production of nitric oxide and distress was seen in the macrophages after exposure to the solid lipid nanoparticles.…”

Section: Discussionmentioning

confidence: 85%

Effect of nanoparticles binding ß-amyloid peptide on nitric oxide production by cultured endothelial cells and macrophages

Orlando¹,

Sesana²,

Rivolta³

et al. 2013

IJN

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Background: As part of a project designing nanoparticles for the treatment of Alzheimer's disease, we have synthesized and characterized a small library of nanoparticles binding with high affinity to the β-amyloid peptide and showing features of biocompatibility in vitro, which are important properties for administration in vivo. In this study, we focused on biocompatibility issues, evaluating production of nitric oxide by cultured human umbilical vein endothelial cells and macrophages, used as models of cells which would be exposed to nanoparticles after systemic administration. Methods: The nanoparticles tested were liposomes and solid lipid nanoparticles carrying phosphatidic acid or cardiolipin, and PEGylated poly(alkyl cyanoacrylate) nanoparticles (PEG-PACA). We measured nitric oxide production using the Griess method as well as phosphorylation of endothelial nitric oxide synthase and intracellular free calcium, which are biochemically related to nitric oxide production. MTT viability tests and caspase-3 detection were also undertaken. Results: Exposure to liposomes did not affect the viability of endothelial cells at any concentration tested. Increased production of nitric oxide was detected only with liposomes carrying phosphatidic acid or cardiolipin at the highest concentration (120 µg/mL), together with increased synthase phosphorylation and intracellular calcium levels. Macrophages exposed to liposomes showed a slightly dose-dependent decrease in viability, with no increase in production of nitric oxide. Exposure to solid lipid nanoparticles carrying phosphatidic acid decreased viability in both cell lines, starting at the lowest dose (10 µg/mL), with increased production of nitric oxide detected only at the highest dose (1500 µg/mL). Exposure to PEG-PACA affected cell viability and production of nitric oxide in both cell lines, but only at the highest concentration (640 µg/mL). Conclusion: Liposomal and PEG-PACA nanoparticles have a limited effect on vascular homeostasis and inflammatory response, rendering them potentially suitable for treatment of Alzheimer's disease. Moreover, they highlight the importance of testing such nanoparticles for production of nitric oxide in vitro in order to identify a therapeutic dose range suitable for use in vivo.

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“…Moreover, after topical application SLNs were able to transfect corneal epithelium [89]. The efficacy of SLNs can be improved by the incorporation of different components, such as, protamine sulfate [88], cell penetration peptides [87], dextran [90], chitosan [91] or hyaluronic acid [92], among others. These ligands act increasing nucleic acid protection, cell internalization or improving the trafficking inside the cells.…”

Section: Lipid-based Vectorsmentioning

confidence: 99%

Treatment of ocular disorders by gene therapy

Solinís

Pozo-Rodríguez

Apaolaza

et al. 2015

European Journal of Pharmaceutics and Biopharmaceutics

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Dextran–protamine–solid lipid nanoparticles as a non-viral vector for gene therapy: In vitro characterization and in vivo transfection after intravenous administration to mice

Cited by 79 publications

References 41 publications

Nanoparticle-mediated delivery of TGF-β1 miRNA plasmid for preventing flexor tendon adhesion formation

Nanoparticle-mediated delivery of TGF-β1 miRNA plasmid for preventing flexor tendon adhesion formation

Effect of nanoparticles binding ß-amyloid peptide on nitric oxide production by cultured endothelial cells and macrophages

Treatment of ocular disorders by gene therapy

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Dextran–protamine–solid lipid nanoparticles as a non-viral vector for gene therapy: In vitro characterization and in vivo transfection after intravenous administration to mice

Cited by 79 publications

References 41 publications

Nanoparticle-mediated delivery of TGF-β1 miRNA plasmid for preventing flexor tendon adhesion formation

Nanoparticle-mediated delivery of TGF-β1 miRNA plasmid for preventing flexor tendon adhesion formation

Effect of nanoparticles binding &szlig;-amyloid peptide on nitric oxide production by cultured endothelial cells and macrophages

Treatment of ocular disorders by gene therapy

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Effect of nanoparticles binding ß-amyloid peptide on nitric oxide production by cultured endothelial cells and macrophages