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

Tibell, Annika; Larsson, Markus; Alvestrand, Anders

doi:10.1007/bf00336647

Cited by 10 publications

(7 citation statements)

References 12 publications

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“…In another example, a Cremophor®EL/ethanol-based cyclosporine (Sandimmune® Injection) was reformulated into nanoemulsion using soybean oil and egg lecithin composition. The studies indicated that a change in the vehicle may reduce the acute nephrotoxic side effects associated with cyclosporine in the Cremophor®EL formulation (18). Alprostadil palmitate, amphotericin B, dexamethasone, flurbiprofen axetil, and vitamins A, D, E, and K are some other examples of therapeutically relevant compounds that have been formulated in nanoemulsions for clinical applications.…”

Section: Introduction-applications Of Nanoemulsions In Drug Deliverymentioning

confidence: 99%

Nanoemulsions in Translational Research—Opportunities and Challenges in Targeted Cancer Therapy

et al. 2014

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Abstract. Nanoemulsion dosage form serves as a vehicle for the delivery of active pharmaceutical ingredients and has attracted great attention in drug delivery and pharmacotherapy. In particular, nanoemulsions act as an excellent vehicle for poorly aqueous soluble drugs, which are otherwise difficult to formulate in conventional dosage forms. Nanoemulsions are submicron emulsions composed of generally regarded as safe grade excipients. Particle size at the nanoscale and larger surface area lead to some very interesting physical properties that can be exploited to overcome anatomical and physiological barriers associated in drug delivery to the complex diseases such as cancer. Along these lines, nanoemulsions have been engineered with specific attributes such as size, surface charge, prolonged blood circulation, target specific binding ability, and imaging capability. These attributes can be tuned to assist in delivering drug/imaging agents to the specific site of interest, based on active and passive targeting mechanisms. This review focuses on the current state of nanoemulsions in the translational research and its role in targeted cancer therapy. In addition, the production, physico-chemical characterization, and regulatory aspects of nanoemulsion are addressed.

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Section: Introduction-applications Of Nanoemulsions In Drug Deliverymentioning

confidence: 99%

Nanoemulsions in Translational Research—Opportunities and Challenges in Targeted Cancer Therapy

et al. 2014

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“…There is a controversy about the effect of this vehicle on the kidney. Most authors studying its effect suggested that it might play a role in the acute nephrotoxicity that seen during CsA infusion (Tibell et al, 1993). This may be explained by the well known anaphylactic reaction to CrEL when given intravenously (Sweetman, 2007).…”

Section: Discussionmentioning

confidence: 99%

Amelioration of chronic cyclosporine A-induced nephrotoxicity by telmisartan in rats

Al-Amran

Hadi²,

Kamoona³

et al. 2011

Afr. J. Pharm. Pharmacol.

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Nephrotoxicity is a major problem of Cyclosporine A (CsA) treatment, despite its beneficial role in organ transplantation and in a variety of immunologic disorders. This study was undertaken to investigate the potential renoprotective role of telmisartan in amelioration of chronic CsA induced nephrotoxicity. The rats were randomized into 4 equal groups. Group 1 received normal saline (control), group 2 received Cremophor EL and ethanol (CsA vehicle), group 3 received CsA 25 mg/kg/day s.c and group 4 received telmisartan 3 mg/kg/day orally in addition to CsA. The rats were pair fed with a standard chow diet throughout the experiment period (8 weeks). CsA nephrotoxicity was assessed in terms of increased S.Cr (from 0.52± 0.16 to 1.29 ± 0.20 mg/ml), blood urea (from 24.69 ± 1.89 to 75.88± 2.33 mg/ml) and serum K (from 3.43 ± 0.18 to 5.23 ± 0.43 meq/l). CsA also caused significant increase (p<0.01) in MDA (from 0.74 ± 0.13 to 2.96 ± 0.43 nmol/mg protein) and significant decrease (p<0.01) in GSH and catalase in renal tissue. Telmisartan failed to restore the altered renal functions. On the other hand, it causes a significant improvement in the histological changes including the tubulointerstitial fibrosis and arteriolopathy (p<0.01). It also caused significant reduction (p<0.01) in CsA-induced oxidative stress. These findings suggested that telmisartan has a promising renoprotective effect against chronic CsA induced nephrotoxicity.

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“…while the infusion of Sandimmune@ was associated with an acute decrease in glomerular filtration (Tibell et al 1993). Infusion of Cremophor@ EL alone was also associated with an acute deterioration in renal function.…”

mentioning

confidence: 91%

“…It is also believed to cause the anaphylactic reactions reported in connection with Sandimmune infusions (S Olesen et al 1978: Kahan et al 1984. A possible alternative to Cremophor@ EL may be to use biologically more acceptable lipids as carriers, and fat emulsions as well as liposomal formulations have been tried experimentally (Smeesters et al 1988;Gorecki et al 1991;Tibell et al 1993).…”

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confidence: 99%

Cyclosporin A in Fat Emulsion Carriers: Experimental Studies on Pharmacokinetics and Tissue Distribution

Tibell

Lindholm

Säwe

et al. 1995

Pharmacology & Toxicology

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In the commercially available intravenous formulation of Cyclosporin A (Sandimmun), polyoxyethylated castor oil (Cremophor EL) is used as a solubilizing agent. We have recently reported that the acute nephrotoxic effect of this preparation was alleviated by replacing Cremophor EL with a soybean oil-based fat emulsion in a rat model. To further explore the potential of fat emulsions as carriers for cyclosporin A, data on the in vivo pharmacokinetics and tissue distribution are required. In this study in pigs, the pharmacokinetics of soybean oil-cyclosporin A was compared to that of Sandimmun. The two formulations seemed bioequivalent, as there were no significant differences in the systemic clearances, volumes of distribution or elimination half-lives. Moreover, the tissue distributions of soybean oil-cyclosporin A and Sandimmun were compared in rats. These studies also included two additional lipid-based carriers: one based on iodized ester of poppy seed oil and the other on a liposomal preparation. The tissue distributions were found to be similar regardless of the carriers used. Fat emulsion carriers seem to offer possibilities for preparing better tolerated intravenous formulations of cyclosporin A while maintaining the same characteristics concerning pharmacokinetics and tissue distribution.

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

Cited by 10 publications

References 12 publications

Nanoemulsions in Translational Research—Opportunities and Challenges in Targeted Cancer Therapy

Nanoemulsions in Translational Research—Opportunities and Challenges in Targeted Cancer Therapy

Amelioration of chronic cyclosporine A-induced nephrotoxicity by telmisartan in rats

Cyclosporin A in Fat Emulsion Carriers: Experimental Studies on Pharmacokinetics and Tissue Distribution

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