Evidence That Liposome Incorporation of Cyclosporine Reduces Its Toxicity and Potentiates Its Ability to Prolong Survival of Cardiac Allografts in Mice

Dc, Górecki; Jakóbisiak, Marek; Kruszewski, Adam M.; Lasek, W

doi:10.1097/00007890-199111000-00002

Cited by 13 publications

(4 citation statements)

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“…Encapsulation in liposomes was shown to reduce nephrotoxicity and to enhance the immune suppressive effect. Mechanistic studies revealed that the increased efficacy is likely to be a consequence of the uptake of the liposomes by macrophages of the MPS in the liver and spleen: cells that play an important role in this type of systemic inflammatory (and immune) disorders [57][58][59].…”

Section: Enhanced Uptake By Mononuclear Phagocyte System Macrophagesmentioning

confidence: 99%

“…Allograft rejection [57][58][59] Tacrolimus Allograft rejection [60][61][62] Extravasation into target tissue Suboptimal concentration at target site Methotrexate Arthritis [78][79][80][81] Superoxide dismutase Arthritis [82,83] Corticosteroids Arthritis [84,85] Encephalomyelitis [86,87] Selective interaction with and uptake by target cells Inability to enter target cells Dexamethasone Hypersensitivity [96] Arthritis Oddly, most of the work with LCLs in inflammatory disorders does not deal with therapeutic agents but imaging agents. LCLs have been successfully labelled with γ-emitting radionuclides such as 99m-technetium and 111-indium and used as a diagnostic tool for the detection of inflammatory and infectious lesions.…”

Section: Cyclosporinmentioning

confidence: 99%

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Liposomes in the treatment of inflammatory disorders

Metselaar

Storm

2005

Expert Opinion on Drug Delivery

112

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This review focuses on the therapeutic utility of liposomes in the treatment of inflammatory disorders, and aims to offer the reader an overview of the in vivo results obtained with liposomally encapsulated anti-inflammatory and immune suppressive drugs. The past 30 years has clearly indicated the added value of liposomes in the search for solutions for the delivery problems encountered. However, only a few liposomal anti-inflammatory therapeutics have entered the clinic. Reasons for the hurdles existing in the translation of promising preclinical findings to clinical studies are discussed.

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Section: Enhanced Uptake By Mononuclear Phagocyte System Macrophagesmentioning

confidence: 99%

Section: Cyclosporinmentioning

confidence: 99%

Liposomes in the treatment of inflammatory disorders

Metselaar

Storm

2005

Expert Opinion on Drug Delivery

112

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“…Luke et al [lo] have also demonstrated that, in the isolated, perfused rat kidney, the administration of Sandimmun infusion substance causes a 63 % decrease in GFR (measured by inulin clearance), while CyA delivered by nontoxicliposomes hasno negativeeffect,despite the same accumulation of CyA in the kidney. Gorecki et al recently published a study showing that the liposomal incorporation of CyA reduced theside effects andincreasedgraft survival in a mouse model [4]. These findings resemble the results achieved in humans by administering amphotericin B in a new vehicle.…”

Section: Resultsmentioning

confidence: 58%

Dissolving intravenous cyclosporin A in a fat emulsion carrier prevents acute renal side effects in the rat

1993

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Cyclosporin A (CyA)-induced nephrotoxicity is still a serious clinical problem. The nephrotoxicity seems to be more pronounced when CyA (solubilized in water with Cremophore EL, as in Sandimmun) is given intravenously than when it is given orally. Using soybean oil in which CyA was dissolved, we prepared an intravenous fat emulsion without an artificial detergent, such as Cremophore EL. The renal effects of our new formula were compared with those of Sandimmun and Cremophore EL in a rat model. CyA in the fat emulsion did not significantly affect the glomerular filtration rate (GFR). Both Sandimmun and Cremophore EL significantly reduced the GFR. These results suggest that a change in the vehicle may obviate the acute nephrotoxic side effects caused by intravenous administration of CyA solubilized by Cremophore EL.

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“…Gorecki et al have obtained increased CyA concentrations in the spleen accompanied by prolonged heart graft survival using a liposomal formulation in mice [4]. Arnoux et al demonstrated prolonged graft survival in a rat model when CyA was administered in small liposomes rather than in a Cremophore-based solution [1].…”

Section: Discussionmentioning

confidence: 99%

Cyclosporin A in fat emulsion carriers: studies on the immunosuppressive potential, using the heterotopic heart transplant model in rats

Tibell

Norrlind²

1994

Transpl Int

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Cyclosporin A (CyA) is an extremely lipophilic drug that needs a solubilizing agent to become soluble in water. In the commercially available intravenous formulation--Sandimmun--Cremophor EL is used for this purpose. It is likely that Cremophor EL contributes to some of the side effects produced by i.v. Sandimmun. We have recently shown that if Cremophor EL is replaced by a soybean oil (SBO)-based fat emulsion carrier, the acute renal side effects following i.v. administration of CyA are avoided in a rat model. It is then important to ascertain whether the use of a fat emulsion carrier alters the immunosuppressive effect of CyA. Moreover, fatty acids can themselves influence the immune system, and both omega-3 and omega-6 fatty acids have been reported to possess immunosuppressive properties. In the present study, the effect on graft survival of i.v. CyA administered in five different formulations, using fat emulsions or liposomes as carriers, was compared to that of conventional Sandimmun infusion substance in the heterotopic heart transplant model in rats. The new formulations tested did not reduce the immunosuppressive effect of CyA. On the contrary, a small but significant increase in graft survival was noted in the groups given CyA in the SBO-based fat emulsion carrier (17.0 +/- 0.82 days) and CyA in liposomes (16.0 +/- 0.63 days) as compared to the results in the Sandimmun-treated group (15.0 +/- 0.58 days: P < 0.01 and P < 0.05, respectively).

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Evidence That Liposome Incorporation of Cyclosporine Reduces Its Toxicity and Potentiates Its Ability to Prolong Survival of Cardiac Allografts in Mice

Cited by 13 publications

References 0 publications

Liposomes in the treatment of inflammatory disorders

Liposomes in the treatment of inflammatory disorders

Dissolving intravenous cyclosporin A in a fat emulsion carrier prevents acute renal side effects in the rat

Cyclosporin A in fat emulsion carriers: studies on the immunosuppressive potential, using the heterotopic heart transplant model in rats

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