Intravenous administration of mannosylated cationic liposome/NFκB decoy complexes effectively prevent LPS‐induced cytokine production in a murine liver failure model

Higuchi, Yuriko; Kawakami, Shigeru; Oka, Machiko; Yabe, Yoshiyuki; Yamashita, Fumiyoshi; Hashida, Mitsuru

doi:10.1016/j.febslet.2006.05.059

Cited by 35 publications

(25 citation statements)

References 32 publications

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“…40,41 The intravenous injection of 'naked' NF-kB decoy ODN in an animal model showed accumulation in the kidney (30% of the dose per g tissue), but little accumulation in other organs. 42 Therefore, alternative delivery methods such as local administration, 43,44 combination use with cationic liposome as a carrier, 40 and physical stimulation by ultrasound wave 45,46 have been reported. In other series of study, we directly injected 'naked' NF-kB decoy ODN into a LM8 tumor mass and examined the biodistribution and the inhibitory effects of the decoy in a murine spontaneous pulmonary metastasis model.…”

Section: Discussionmentioning

confidence: 99%

Transfection of NF-κB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma

et al. 2010

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Nuclear factor-kappa B (NF-kB) has a pivotal role in the progression and distant metastasis of cancers, including malignant bone tumors. To inhibit NF-kB activation, a new molecular therapy using synthetic double-stranded oligodeoxynucleotide (ODN) as a 'decoy' cis element against NF-kB has been developed. To determine whether pulmonary metastasis of osteosarcoma is reduced by inhibiting the action of NF-kB, NF-kB decoy ODN was transfected into the nuclei of murine osteosarcoma cells with high pulmonary metastatic potential, the LM8 cell line, using a three-dimensional alginate spheroid culture model. An in vitro study demonstrated the successful transfection of LM8 cells cultured in alginate beads by 'naked' NF-kB decoy ODN and that the activation of NF-kB signaling was significantly suppressed. Tumor growth was not affected by transfection of NF-kB decoy ODN, however, the expression of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM-1) mRNA was markedly decreased. Furthermore, the transfection of 'naked' NF-kB decoy ODN effectively suppressed pulmonary metastasis in an in vivo alginate bead transplantation model. Our results suggest that NF-kB has a central and specific role in the regulation of tumor metastasis and could be a molecular target for development of anti-metastatic treatments for osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

Transfection of NF-κB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma

et al. 2010

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“…We have reported previously macrophage-selective targeting carriers composed of novel mannosylated cholesterol derivatives, cholesten-5-yloxy-N-(4-((1-imino-2-D-thiomannosylethyl)amino)butyl)formamide (Man-C4-Chol), as a ligand for mannose receptors (Kawakami et al, 2000a;Hattori et al, 2006;Higuchi et al, 2006;Yeeprae et al, 2006). We have demonstrated the efficient targeting of mannosylated liposomes (Man-liposomes) to alveolar macrophages after intratracheal administration in rats (Wijagkanalan et al, 2008).…”

Section: Inhalation Of Lipopolysaccharide (Lps)mentioning

confidence: 99%

Enhanced Anti-Inflammation of Inhaled Dexamethasone Palmitate Using Mannosylated Liposomes in an Endotoxin-Induced Lung Inflammation Model

Wijagkanalan¹,

Higuchi²,

Kawakami³

et al. 2008

Molecular Pharmacology

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Inhalation of bacterial endotoxin induces pulmonary inflammation by activation of nuclear factor B (NFB), production of cytokines and chemokines, and neutrophil activation. Although glucocorticoids are the drugs of choice, administration of free drugs results in adverse effects as a result of a lack of selectivity for the inflammatory effector cells. Because alveolar macrophages play a key role in the inflammatory response in the lung, selective targeting of glucocorticoids to alveolar macrophages offers efficacious pharmacological intervention with minimal side effects. We have demonstrated previously the selective targeting of mannosylated liposomes to alveolar macrophages via mannose receptor-mediated endocytosis after intratracheal administration. In this study, the anti-inflammatory effects of dexamethasone palmitate incorporated in mannosylated liposomes (DPML) at 0.5 mg/kg via intratracheal administration were investigated in lipopolysaccharide-induced lung inflammation in rats. DPML significantly inhibited tumor necrosis factor ␣, interleukin-1␤, and cytokine-induced neutrophil chemoattractant-1 levels, suppressed neutrophil infiltration and myeloperoxidase activity, and inhibited NFB and p38 mitogen-activated protein kinase activation in the lung. These results prove the value of inhaled mannosylated liposomes as powerful targeting systems for the delivery of anti-inflammatory drugs to alveolar macrophages to improve their efficacy against lung inflammation. Inhalation of lipopolysaccharide (LPS), which is a component of Gram-negative bacteria presenting as an environment pollutant, contributes to inflammation in the lung. The downstream signaling pathways after LPS stimulation include the activation of alveolar macrophages, which are key effector cells to release proinflammatory cytokines including tumor necrosis factor ␣ (TNF␣), interleukin-1␤ (IL-1␤) (Ulich et al., 1991), chemokines such as cytokine-induced neutrophil chemoattractant-1 (CINC-1) (Ulich et al., 1995), and activation of nuclear factor B (NFB) and p38 mitogen-activated protein kinase (p38MAPK). Thereafter, neutrophils are recruited into the lung and release protease enzymes, which trigger lung injury. Corresponding to these studies, depletion of alveolar macrophages by liposomal clodronate treatment completely suppressed the downstream signaling after LPS stimulation (Koay et al., 2002). These results indicate that alveolar macrophages play a key role in the inflammation to release proinflammatory cytokines and chemokines after LPS stimulation.Glucocorticoids (GCs) are the drugs of choice for treatment of lung inflammation via systemic or local administration. Although inhalation of free GC is a promising therapy with less systemic toxicity, the therapeutic efficacy has been ques-

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“…formamide (Man-C4-Chol), a galactosylated cholesterol derivative, to prepare mannosylated liposomes [179]. To deliver drugs into macrophage-and/or dendritic cell in various tissues, we investigated various administration routes including intravenous [179,[192][193][194][195][196][197], intraperitoneal [198][199][200][201], and intratracheal [202,203] administration.…”

Section: Development Of Mannosylated Liposomesmentioning

confidence: 99%

Glycosylation-mediated targeting of carriers

Kawakami

Hashida

2014

Journal of Controlled Release

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For safe and effective therapy, drugs should be delivered selectively to their target tissues or cells at an optimal rate. Drug delivery system technology maximizes the therapeutic efficacy and minimizes unfavorable drug actions by controlling their distribution profiles. Ligand-receptor binding is a typical example of specific recognition mechanisms in the body; therefore, ligand-modified drug carriers have been developed for active targeting based on receptor-mediated endocytosis. Among the various ligands reported thus far, sugar recognition is a promising approach for active targeting because of their high affinity and expression. Glycosylation has been applied for both macromolecular and liposomal carriers for cell-selective drug targeting.Recently, the combination of ultrasound exposure and glycosylated bubble liposomes has been developed. In this review, recent advances of glycosylation-mediated targeted drug delivery systems are discussed.

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Intravenous administration of mannosylated cationic liposome/NFκB decoy complexes effectively prevent LPS‐induced cytokine production in a murine liver failure model

Cited by 35 publications

References 32 publications

Transfection of NF-κB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma

Transfection of NF-κB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma

Enhanced Anti-Inflammation of Inhaled Dexamethasone Palmitate Using Mannosylated Liposomes in an Endotoxin-Induced Lung Inflammation Model

Glycosylation-mediated targeting of carriers

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