Disease relevance of Poloxalkol

• ANCOVA demonstrated that the 48-hour infusion of poloxamer 188 reduced myocardial infarct size independent of differences in collateral blood flow (P = .002 versus control) [1].
• Poloxamer 188 was well tolerated without adverse hemodynamic effects or significant organ toxicity [2].
• However, although both EVAc and Pluronic release of c-myb antisense oligonucleotide sequences inhibited intimal hyperplasia 2 weeks after injury, only the more prolonged EVAc matrix release of antisense oligonucleotide to c-myc was effective [3].
• Neither Fluosol nor Pluronic caused mortality without E coli [4].
• The purpose of the studies we report here was to determine if Fluosol or Pluronic might also reduce in vivo neutrophil migration and impair host resistance to bacterial infection [4].

Psychiatry related information on Poloxalkol

• Thermoreversible nasal gels of Vitamin B(12) using pluronic PF 127 were aimed to improve absorption and patient compliance [5].
• We examined satiation after intraduodenal infusion of triglyceride with or without Pluronic L-81 (L-81) in rats [6].

High impact information on Poloxalkol

• By electron microscopy, enterocytes from Pluronic- and fenfluramine-treated animals exhibited a two- to threefold increase in large intracellular cytoplasmic lipid globules and the appearance of lamellae in apposition, with a marked decrease in the number of surfactant-like particles overlying the brush border [7].
• Antisense c-myc applied in a pluronic gel to the arterial adventitia reduced peak c-myc expression by 75% and significantly reduced neointimal formation at 14 d, compared with sense c-myc and gel application alone [8].
• A parallel decline (60%) in alkaline phosphatase activity occurred in the lamina propria of Pluronic-treated animals [7].
• CONCLUSIONS: Adjunctive therapy with poloxamer 188 resulted in substantial benefit in this randomized trial, including significantly smaller infarcts, greater myocardial salvage, better left ventricular function, and a lower incidence of in-hospital reinfarction [2].
• Reduction in reperfusion-induced myocardial necrosis in dogs by RheothRx injection (poloxamer 188 N.F.), a hemorheological agent that alters neutrophil function [1].

Chemical compound and disease context of Poloxalkol

• Before reperfusion, rabbits received a 25-ml/kg infusion of 1) Fluosol; 2) poloxamer 188 (equivalent % w/v to Fluosol, 675 mg/kg body weight); or 3) 5% dextrose (control) [9].
• Treatment of toxoplasmic encephalitis with CRL 8131 plus an ineffective dose of atovaquone reduced the inflammation and numbers of Toxoplasma gondii cysts in the brain [10].
• OBJECTIVE: To study the toxicity and activity of two new amphotericin B formulations: poly(epsilon-caprolactone) nanospheres coated with poloxamer 188 (AmB-NP) and mixed micelles with the same surfactant (AmB-MM) [11].
• As a result, the MDR subline demonstrated much higher response ("hypersensitivity") to the daunorubicin/ Pluronic compared to that of the non-MDR cells [12].
• The chemosensitizing effect of Pluronic P85 block copolymer were studied using two human ovarian carcinoma sublines: the glycoprotein P (P-gp) multidrug resistant (MDR) SKVLB cells and non-MDR SKOV3 cells [12].

Biological context of Poloxalkol

• In vitro studies demonstrated that at concentrations comparable to those achieved in vivo, poloxamer 188 inhibited neutrophil chemotaxis [1].
• The acute release of antisense oligonucleotides from the Pluronic gels reduced in vitro cell growth 54.8% with c-myc and 56.9% with c-myb [3].
• Neither Fluosol nor Pluronic changed sickle or normal cell shape, mean cell volume, mean cell density, or cell density distribution [13].
• Furthermore, Pluronic F68 NF restored resealing when exocytosis was blocked by tetanus toxin [14].
• Effects of poloxamer 407 on transfection time and percutaneous adenovirus-mediated gene transfer in native and stented vessels [15].

Anatomical context of Poloxalkol

• In studies using cultured skeletal muscle cells, poloxamer 188 (P188; an 8.4-kDa nonionic surfactant) blocks, and neutral dextran (10.1 kDa) substantially retards, carboxyfluorescein release from electropermeabilized cell membranes [16].
• CONCLUSIONS: A 48-hour infusion of poloxamer 188 reduced myocardial infarct size and improved left ventricular function in this dog model of 90 minutes of coronary artery occlusion and 72 hours of reperfusion [1].
• Pluronic did not alter reticuloendothelial system (RES) clearance function [4].
• Within 24 hours of injury, Pluronic-based release of c-myc antisense oligomers reduced mRNA levels in the tunica media 2.5-fold and immunocytochemical identification of c-myc expression by 98.8% [3].
• Using x-ray scattering measurements we have quantitatively determined the effect of poloxamer 188 (P188), a polymer known to seal damaged membranes, on the structure of lipid monolayers [17].

Associations of Poloxalkol with other chemical compounds

• Poloxamer 188, formulated as RheothRx Injection (Burroughs Wellcome Co), was given as a 75 mg/kg IV bolus 15 minutes before reperfusion followed by a 150 mg.kg-1.h-1 continuous IV infusion for 4 hours (n = 13) or 48 hours (n = 13); control dogs (n = 12) received saline for 48 hours [1].
• Dox was encapsulated within stabilized Pluronic micelles and administered weekly i.v. to the rats starting 6 weeks after the tumor inoculations [18].
• We have shown that class I-restricted CTLs can be induced by injecting soluble antigens mixed in an antigen formulation (AF) that consists of squalane, Tween 80, and Pluronic L121 (S. Raychaudhuri et al., Proc. Natl. Acad. Sci. USA, 89: 8308-8312, 1992) [19].
• In an effort to improve the efficacy of antisense delivery, we evaluated polyethyleneimine (PEI, 2 kDa) alone or grafted with nonionic amphiphilic block copolymer Pluronic (P85) as a carrier for Ku86 antisense oligonucleotide (ASO) delivery [20].
• RESULTS: TPGS, but not Poloxamer 188, inhibited the P-gp-mediated talinolol transport in Caco-2 cells [21].

Gene context of Poloxalkol

• Inhibitory effect of the reversal agents V-104, GF120918 and Pluronic L61 on MDR1 Pgp-, MRP1- and MRP2-mediated transport [22].
• PURPOSE: This study evaluated the chemosensitizing effects of Pluronic P85 (P85) on cells expressing multidrug resistance-associated proteins, MRPI and MRP2 [23].
• Accumulation of chylomicrons, very low density lipoproteins (VLDL), and cholesterol-enriched remnants in the Pluronic treated mice and ApoE deficient mice did not inhibit tumor growth, even though mice in all three models were equally hypercholesterolemic [24].
• Either PTHrP-(1-34) or PTHrP-(7-34), a PTH/PTHrP receptor antagonist, suspended in pluronic F-127 gel was locally applied around the rat femoral artery [25].
• Inhibition of multidrug resistance-associated protein (MRP) functional activity with pluronic block copolymers [26].

Analytical, diagnostic and therapeutic context of Poloxalkol

• INTERVENTION: Patients were randomly assigned to receive an intravenous infusion of purified poloxamer 188, 100 mg/kg for 1 hour followed by 30 mg/kg per hour for 47 hours (n = 127), or a matching volume of saline placebo (n = 128) [27].
• Total particle content (measured by an ELISA using antiserum against purified particle) after Pluronic treatment was decreased in mucosal scrapings, lamina propria, and serum by 16, 22, and 29% at 3 h and by 33, 40, and 8%, respectively, at 5 h after fat feeding [7].
• Although the mechanisms are unproven, poloxamer 188 treatment may accelerate thrombolysis, reduce reocclusion, and ameliorate reperfusion injury [2].
• The treated and control groups had comparable baseline characteristics, time to thrombolytic administration, and time to treatment with poloxamer 188 or placebo [2].
• BACKGROUND: RheothRx (poloxamer 188) is a surfactant with hemorheological and antithrombotic properties that reduces myocardial reperfusion injury in animal models of myocardial infarction [2].

References