Nanocomposites of lung surfactant and biodegradable cationic nanoparticles improve transfection efficiency to lung cells

Nguyen, Juliane; Reul, Regina; Betz, Thomas; Dayyoub, Eyas; Schmehl, Thomas; Gessler, Tobias; Bakowsky, Udo; Seeger, Werner; Kissel, Thomas

doi:10.1016/j.jconrel.2009.07.017

Cited by 50 publications

(32 citation statements)

References 29 publications

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“…Kissel and co-workers also recently reported on the interaction of a natural lung-derived surfactant (Alveofact TM ) with polymeric nucleic acid nanoparticles in a lung epithelial cell line [31,32]. In contrast to our data, they observed an enhanced cellular uptake of pDNA [31] or siRNA [32] after addition of the surfactant. This effect was attributed to hydrophobic interactions or a membrane fusion process stimulated by the presence of phospholipids on the nanoparticle surface [32].…”

Section: Discussioncontrasting

confidence: 99%

The Influence of Natural Pulmonary Surfactant on The Efficacy of siRNA-Loaded Dextran Nanogels

et al. 2013

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Aims: Topical administration of small interfering RNA (siRNA) nanocarriers is a promising approach in the treatment of pulmonary disorders. Pulmonary surfactant, covering the entire alveolar surface of mammalian lungs, will be one of the first interfaces that siRNA nanocarriers encounter upon inhalation therapy. Therefore, it is of outstanding importance to evaluate the impact of pulmonary surfactant on the performance of siRNA nanocarriers. Materials & Methods: The effect of natural lung-derived surfactants on the siRNA delivery capacity of dextran nanogels (DEX-NGs) is evaluated in vitro using flow cytometry and confocal microscopy.

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Section: Discussioncontrasting

confidence: 99%

The Influence of Natural Pulmonary Surfactant on The Efficacy of siRNA-Loaded Dextran Nanogels

et al. 2013

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“…The characterization of polyanhydride nanoparticles before and after surface modification was consistent with previous studies (6,17,18). The change in the ζ-potential from negative to positive charge after linker attachment can be beneficial for enhanced cellular uptake, as reported previously (50,51). In addition, carbohydrate functionalization is known to enhance both the APC activation in vitro (6,17,18) and the therapeutic efficacy of drug delivery (4).…”

Section: Discussionsupporting

confidence: 88%

“…However, the respiratory system is also a more delicate environment, and parameters such as particle size (61)(62)(63), charge (2,50,51), chemistry (9,33), and material (12,64) affect deposition, distribution, and biocompatibility. In previous work, a single intranasal administration of nonfunctionalized polyanhydride nanovaccines demonstrated the ability to induce protective immunity upon lethal challenge (9,20,65).…”

Section: Discussionmentioning

confidence: 99%

Safety and Biocompatibility of Carbohydrate-Functionalized Polyanhydride Nanoparticles

Vela-Ramirez

Goodman

Boggiatto

et al. 2014

AAPS J

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ABSTRACT. Carbohydrate functionalization of nanoparticles allows for targeting of C-type lectin receptors. This family of pattern recognition receptors expressed on innate immune cells, such as macrophages and dendritic cells, can be used to modulate immune responses. In this work, the in vivo safety profile of carbohydrate-functionalized polyanhydride nanoparticles was analyzed following parenteral and intranasal administration in mice. Polyanhydride nanoparticles based on 1,6-bis-(pcarboxyphenoxy)hexane and 1,8-bis-(p-carboxyphenoxy)-3,6-dioxaoctane were used. Nanoparticle functionalization with di-mannose (specifically carboxymethyl-α-D-mannopyranosyl-(1,2)-Dmannopyranoside), galactose (specifically carboxymethyl-β-galactoside), or glycolic acid induced no adverse effects after administration based on histopathological evaluation of liver, kidneys, and lungs. Regardless of the polymer formulation, there was no evidence of hepatic or renal damage or dysfunction observed in serum or urine samples. The histological profile of cellular infiltration and the cellular distribution and kinetics in the lungs of mice administered with nanoparticle treatments followed similar behavior as that observed in the lungs of animals administered with saline. Cytokine and chemokine profiles in bronchoalveolar lavage fluid indicated surface chemistry dependence on modest secretion of IL-6, IP-10, and MCP-1; however, there was no evidence of any deleterious histopathological changes. Based on these analyses, carbohydrate-functionalized nanoparticles are safe for in vivo applications. These results provide foundational information towards the evaluation of the capabilities of these surface-modified nanoparticles as vaccine delivery formulations.

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“…In contrast, a preferential uptake of negatively charged particles into immortalized alveolar epithelial type 1 cells has been found [47]. Surface charge as an important parameter in biological activity of nanoparticles has been supported also by other authors [12,[48][49][50][51]. However, a mechanical hindrance of MNPs uptake cannot be excluded.…”

Section: Discussionmentioning

confidence: 90%

The intensity of internalization and cytotoxicity of superparamagnetic iron oxide nanoparticles with different surface modifications in human tumor and diploid lung cells

Mesárošová

Cĭampor²,

Závišová³

et al. 2012

neo

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The human lung adenocarcinoma epithelial (A549) cells and the human embryo lung (HEL 12469) cells were used to investigate the uptake and cytotoxicity of magnetite nanoparticles (MNPs) with different chemically modified surfaces. MNPs uptake was an energy-dependent process substantially affected by the serum concentration in the culture medium. Internalized MNPs localized in vesicle-bound aggregates were observed in the cytoplasm, none in the nucleus or in mitochondria. All MNPs induced a dose-and time-dependent increase in cytotoxicity in both human lung cell lines. The cytotoxicity of MNPs increased proportionally with the particle size. Since the cytotoxicity of MNPs was nearly identical when the doses were equalized based on particle surface area, we suppose that the particle surface area rather than the surface modifications per se underlay the cytotoxicity of MNPs. In general, higher internalized amount of MNPs was found in HEL 12469 cells compared with A549 cells. Accordingly, the viability of the human embryo lung cells was reduced more substantially than that of the adenocarcinoma lung cells. The weak MNPs uptake into A549 cells might be of biomedical relevance in cases where MNPs should be used as nanocarriers for targeted drug delivery in tumor tissue derived from alveolar epithelial cells.

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Nanocomposites of lung surfactant and biodegradable cationic nanoparticles improve transfection efficiency to lung cells

Cited by 50 publications

References 29 publications

The Influence of Natural Pulmonary Surfactant on The Efficacy of siRNA-Loaded Dextran Nanogels

The Influence of Natural Pulmonary Surfactant on The Efficacy of siRNA-Loaded Dextran Nanogels

Safety and Biocompatibility of Carbohydrate-Functionalized Polyanhydride Nanoparticles

The intensity of internalization and cytotoxicity of superparamagnetic iron oxide nanoparticles with different surface modifications in human tumor and diploid lung cells

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