Disease relevance of Polysorbate 80

• Polysorbate 80 hypersensitivity [1].
• Furthermore, it is not formulated with polyethylene glycol, polysorbate 80 (Tween; ICI Americas, Wilmington, DE), and ethanol, and does not cause acidosis when given at high doses [2].
• Here, we investigated the biodistribution in the brain and in the body of poly(butyl-2-cyano[3-(14)C]acrylate) NP ([(14)C]-PBCA NP), polysorbate 80 (PS 80)-coated [(14)C]-PBCA NP, DOX-loaded [(14)C]-PBCA NP in glioblastoma 101/8-bearing rats after i.v. injection [3].
• The method was subsequently used to measure concentrations of docetaxel and polysorbate 80 in plasma samples in support of a project to assess the influence of polysorbate 80 concentrations on the disposition and toxicity profile of docetaxel in cancer patients receiving Taxotere [4].
• 4. Hemolysis testing as an in vitro assay indicated that LCC was safer than Polysorbate 80 (TO-10M) as intravenous surfactant in terms of induction of membrane damage [5].

High impact information on Polysorbate 80

• Here, we used rat aortic rings and human umbilical vein endothelial cells to evaluate the influence of their formulation vehicles Cremophor EL and polysorbate 80, as well as serum binding proteins on taxane-mediated antiangiogenesis [6].
• Intravenous amiodarone has been implicated in acute hepatic disease on four previous occasions, but it is suggested that polysorbate 80, an organic surfactant added to the intravenous infusion, is a more likely cause of this complication [7].
• Unbound clearance varied 8.5-fold; polysorbate 80 exhibited mean (+/-SD) C max , AUC, and clearance values of 451 +/- 221 microg/mL, 528 +/- 217 microg/mL . h, and 8.18 +/- 3.66 L/h, respectively; and clearance varied 6.7-fold [8].
• Clinical pharmacokinetics of unbound docetaxel: role of polysorbate 80 and serum proteins [9].
• OBJECTIVE: Our objectives were to study the extent of docetaxel binding to plasma in the presence and absence of its excipient, polysorbate 80 (Tween 80; Imperial Chemical Industries PLC, London, United Kingdom), in vitro and to evaluate the pharmacokinetics of unbound docetaxel in vivo [9].

Chemical compound and disease context of Polysorbate 80

• CONCLUSIONS: A non specific permeabilization of the BBB, probably related to the toxicity of the carrier, may account for the CNS penetration of dalargin associated with PBCA NP and polysorbate 80 [10].
• Poly(butyl cyanoacrylate) nanoparticles coated with poloxamer 188 (Pluronic(R) F68) and also, as shown previously, polysorbate 80 (Tween(R) 80) considerably enhance the anti-tumour effect of doxorubicin against an intracranial glioblastoma in rats [11].
• Toxicological studies of doxorubicin bound to polysorbate 80-coated poly(butyl cyanoacrylate) nanoparticles in healthy rats and rats with intracranial glioblastoma [12].
• Therefore: (a) canine models for studying the antiarrhythmic actions of commercial intravenous amiodarone would produce results complicated by severe hypotension; and (b) polysorbate 80 is not an inert substance, but is a potent cardiac depressant [13].
• DISCUSSION: Both etoposide and its excipient (polysorbate 80) are suspected of causing hypersensitivity reactions [14].

Biological context of Polysorbate 80

• Although vasodilatation of short duration caused by its solvent, polysorbate 80, also occurs, the overall cardiovascular changes are caused by the direct, intrinsic haemodynamic effects of amiodarone alone [15].
• While the results of previous human studies have been rather variable, our investigations suggest that the cardiovascular changes following intravenous amiodarone include an early and usually short reduction of systemic and coronary vascular resistance, which may be partially due to the vasodilating properties of the solvent, polysorbate 80 [15].
• Muscle exposed to polysorbate 80 (10 to 80 micrograms ml-1) showed a concentration-dependent lengthening of action potential duration (APD) but no detectable change in Vmax [16].
• These results further support the hypothesis that the mechanism of blood-brain barrier transport of drugs by polysorbate 80-coated nanoparticles is one of endocytosis followed by possible transcytosis [17].
• The results indicate that neither competitor displaced significant amounts of the parabens from their binding sites on polysorbate 80 [18].

Anatomical context of Polysorbate 80

• 2. The action of oleic acid is not a pathological phenomenon due to lesions of the gut mucosa because isotonic solutions of Na oleate dispersed into polysorbate 80 or olive oil (rich in oleic acid) plus pancreatic juice have the same effect [19].
• With cells from these species we were able to show that polysorbate 80-coated nanoparticles were taken up by brain endothelial cells much more rapidly and in significantly higher amounts (20-fold) than uncoated nanoparticles [20].
• Doxorubicinol was measured also in the cytosol of human myocardial strips incubated in plasma and exposed to doxorubicin in the absence or presence of paclitaxel or docetaxel and their clinical vehicles Cremophor EL or polysorbate 80 [21].
• The experiments reported here suggest that polysorbate 80 has a direct effect on the blood-brain barrier leading to the increased uptake of MTX, which is evident following IV administration [22].
• CONCLUSIONS: Polysorbate 80 promoted chylomicron secretion in Caco-2 cells and counteracted the inhibitory effects of other surfactants [23].

Associations of Polysorbate 80 with other chemical compounds

• It was reported that nanoparticles with polysorbate 80 (Tween 80, T-80) coating represented tools used for delivering drugs to brain [24].
• The formulation consisted of dalargin bound to poly(butyl cyanoacrylate) nanoparticles by sorption, coated with polysorbate 80 [25].
• CONCLUSIONS: Polysorbate 80-coated PBCA nanoparticles loaded with loperamide enabled the transport of loperamide to the brain [26].
• In vitro-in-vivo studies showed that the liposomal encapsulation of loxapine resulted in significant (P < 0.05) reduction in myotoxicity (80% in vitro and 60% in vivo) compared to the commercially available formulation which contains propylene glycol (70% V/V) and polysorbate 80 (5% W/V) prepared at equal concentration [27].
• It was shown that the presence of polysorbate 80 (Tween(R) 80) in the nanoparticle formulation significantly enhanced the cytotoxicity, whereas poloxamer 188 (Pluronic(R) F68) and poloxamine 908 (Tetronic(R) 908) had a negligible influence [28].

Gene context of Polysorbate 80

• The results show that only dalargin or loperamide-loaded nanoparticles coated with polysorbate 80 and/or with apolipoprotein B or E were able to achieve an antinociceptive effect [29].
• CONCLUSION: At concentrations of PBCA nanoparticles and polysorbate-80 that achieve significant drug delivery to the brain, there is little in vivo or in vitro evidence to suggest that a generalized toxic effect on the BBB is the primary mechanism for drug delivery to the brain [30].
• We have substituted cholesterol with fatty alcohols in niosomes containing polyglyceryl-3-di-isostearate (PGDS) and polysorbate-80 (PS-80) to explore their membrane-stabilizing property via permeation studies [31].
• Rapid esterase-sensitive breakdown of polysorbate 80 and its impact on the plasma pharmacokinetics of docetaxel and metabolites in mice [32].
• RESULTS: For 2001 to 2003, the PRCA incidence rate for patients with subcutaneous exposure to Eprex in prefilled syringes with polysorbate 80 and uncoated rubber stoppers (leachates present) was 4.61/10,000 patient years (95% CI 3.88-5.43) versus 0.26/10,000 patient years (95% CI 0.007-1.44) for syringes with coated stoppers (leachates absent) [33].

Analytical, diagnostic and therapeutic context of Polysorbate 80

• In five sheep, lung injury was induced by lavage with 0.2% polysorbate 80 in saline [34].
• Oral administration of 1 at 2 mg/kg in a 3% polysorbate 80 solution enhanced both the rate and the extent of absorption of the compound [35].
• A simple and fast method for the analysis of polysorbate 80 in pharmaceutical formulations was developed using high-performance liquid chromatography with evaporative light scattering detection (ELSD) [36].
• A quick HPLC method is reported for the analysis of polysorbate 80 in pharmaceutical suspensions [37].
• None of the approaches for further altering the suppressor cell/helper T-cell balance nor changes to the standard formulation by lyophilization or use of polysorbate 80 had any impact on antibody titers [38].

References