Liposomal retention of a modified anti-inflammatory steroid

Shaw, Ina; Knight, Christopher G.; Dingle, J. T.

doi:10.1042/bj1580473

Cited by 71 publications

(20 citation statements)

References 7 publications

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“…Therefore, the effect of charge difference of these neutral liposomes DPBL and DPML, which is due to the positive charge of the Man-C4-Chol structure itself, on their uptake is excluded. Furthermore, the incorporated DP was stably retained in these liposomal formulations after a 48-h incubation correlated with a previous study involving the high retention of steroid palmitate in liposomes (Shaw et al, 1976, Teshima et al, 2004. These results confirm the stability of the liposomal formulations of DP for in vitro studies and intratracheal application in rats.…”

Section: Discussionsupporting

confidence: 76%

“…There are several reports about the application of liposomes to incorporate dexamethasone (Dex), a potent GC, for lung inflammation by intratracheal (i.t.) administration (Tremblay et al, 1993;Suntres and Shek, 2000); however, difficulties in controlling the drug incorporation and retention in liposomes have been reported (Shaw et al, 1976). Benameur et al (1993) demonstrated that dexamethasone palmitate (DP), which is more lipophilic than Dex, was inserted in the lipid bilayer and showed significant encapsulation and retention in the liposomes.…”

Section: Inhalation Of Lipopolysaccharide (Lps)mentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 76%

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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“…Cortisol palmitate (CP) was obtained from ICI Pharmaceuticals Division, Macclesfield, Cheshire, UK. 3H-Cortisol palmitate was prepared according to the method of SHAW et al [10]. J4C-Cholesteryl oleate was obtained from New England Nuclear, Boston, Massachusetts.…”

Section: Methodsmentioning

confidence: 99%

“…Unfortunately, these effects are accompanied by serious dose-related toxic effects, which essentially restrict the use of steroids as anti-inflammatory agents to potentially life-threatening diseases, characterized by inflammation without infection. SHAW et al [10] have-shown that the palmitate ester of cortisol forms stable liposomes with dipalmitoyl phosphatidyl choline (DPPC). These liposomes were shown to have enhanced anti-inflammatory effects, compared to free cortisol, when injected directly into the knees of rabbits with an experimentally-induced arthritis [ 1 1].…”

Section: Introductionmentioning

confidence: 99%

Cortisol palmitate liposomes: Enhanced anti-inflammatory effect in rats compared with free cortisol

et al. 1982

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“…Furthermore, palmitate corticosteroid derivatives have also been studied since the late 1970s, with cortisol palmitate, prednisolone palmitate, and dexamethasone palmitate having been loaded into liposomes. [53][54][55] In our case, we loaded 5% molar concentration of PP into our liposomes with a In both cases (HRECs and HAECs) cells were exposed to free PH (25 lM) or PH loaded into either EPCR-targeting liposomes (EPCR-NL1), EPCR-targeting liposomes with PP in the membrane (EPCR-NL2), or nontargeting liposomes (P-NL1). The cells were subjected to the different treatments for 4 hours, then washed, and supernatants were collected 24 hours and 48 hour after the exposure.…”

Section: Discussionmentioning

confidence: 99%

Endothelial Protein C–Targeting Liposomes Show Enhanced Uptake and Improved Therapeutic Efficacy in Human Retinal Endothelial Cells

Arta

Eriksen

Melander

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To determine whether human retinal endothelial cells (HRECs) express the endothelial cell protein C receptor (EPCR) and to realize its potential as a targeting moiety by developing novel single and dual corticosteroid-loaded functionalized liposomes that exhibit both enhanced uptake by HRECs and superior biologic activity compared to nontargeting liposomes and free drug.METHODS. EPCR expression of HRECs was investigated through flow cytometry and Western blot assays. EPCR-targeting liposomes were developed by functionalizing EPCR-specific antibodies onto liposomes, and the uptake of liposomes was assessed with flow cytometry and confocal laser scanning microscopy. The therapeutic potential of EPCR-targeting liposomes was determined by loading them with prednisolone either through bilayer insertion and/or by remote loading into the aqueous core. The carrier efficacy was assessed in two ways through its ability to inhibit secretion of interleukins in cells stimulated with high glucose and angiogenesis in vitro by using an endothelial cell tube formation assay. RESULTS.HRECs express EPCR at a similar level in both human aortic and umbilic vein endothelial cells. The EPCR-targeting liposomes displayed at least a 3-fold higher uptake compared to nontargeting liposomes. This enhanced uptake was translated into superior antiinflammatory efficacy, as the corticosteroid-loaded EPCR-targeting liposomes significantly reduced the secretion of IL-8 and IL-6 and inhibited the development of cell tube formations in contrast to nontargeting liposomes. CONCLUSIONS.We show that HRECs express EPCR and this receptor could be a promising nanomedicine target in ocular diseases where the endothelial barrier of the retina is compromised.

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Liposomal retention of a modified anti-inflammatory steroid

Cited by 71 publications

References 7 publications

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

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

Cortisol palmitate liposomes: Enhanced anti-inflammatory effect in rats compared with free cortisol

Endothelial Protein C–Targeting Liposomes Show Enhanced Uptake and Improved Therapeutic Efficacy in Human Retinal Endothelial Cells

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