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5 recordsLinked to original sources
PubMed1979

Relationships between poloxamer structure and the solubilization of some para-substituted acetanilides.

Saturation solubilities of several para-substituted acetanilides have been measured at 37 degrees C in aqueous solutions of structurally related polyoxyethylene-polyoxypropylene block copolymers-poloxamers L62, L63, L64, P65 and F68. These poloxamers differ only in the amount of ethylene oxide in the hydrophil. Solubilities increased with increasing poloxamer concentration. As the oxyethylene chain length of the poloxamer increased, then the solubilizing capacity per equivalent of oxyethylene decreased. The moles of acetanilide derivative solubilized per mole of poloxamer increased with poloxamer oxyethylene content in the case of the less hydrophobic acetanilides but was invariant in the more hydrophobic ones. The solubilizing capacities have been discussed in terms of the inter-relationships between the hydrophobic nature of the solubilizate and solubilizer and the site of solubilization on the poloxamer molecule.

Acetanilides↗
PubMed1979

Biological effectiveness, in goldfish, of some p-substituted acetanilides alone and in the presence of poloxamers.

The death times of goldfish have been measured in aqueous solutions containing different concentrations of p-substituted acetanilides alone or in the presence of poloxamers. Plots of reciprocal death time versus concentration were linear with a positive concentration intercept, the minimum effective concentration (MEC). The MEC values were directly related to the pi value (hydrophobic-lipophilic constant) of the functional group on the acetanilide indicating that activity is directly related to lipophilicity. Slopes of reciprocal death time versus drug concentration were linearly related to pi values but there was no direct dependence. The presence of poloxamers in aqueous acetanilide solutions reduced the goldfish death time. The effect of the poloxamers is believed to be one of rendering the goldfish membrane more permeable to drugs.

Acetanilides↗
PubMedDate not supplied

Disposition in rats of a polyoxypropylene-polyoxyethylene copolymer used in plasma fractionation.

A polyoxypropylene-polyoxyethylene block copolymer of about 4750 daltons (Poloxamer 108, Pluronic F-38) used in a new protein fractionation procedure may be infused into patients receiving therapeutic plasma fractions. We studied the disposition and pharmacokinetics of Poloxamer 108 in rats as an initial step towards understanding its behavior in man. After iv administration in rats, about 94% of 7 or 100 mg/kg doses of ethylene-14C-labeled polymer was excreted in the urine in 3 days. About 6% of the label appeared in feces. Erythrocyte membranes were not permeable to the polymer, and only the parent compound was demonstrable in urine. Twenty hours after dosing, small residues were detectable only in the kidney, liver, small intestine, and carcass. The third phase of the plasma disappearance pattern was evident only at the larger dose, but plasma disappearance kinetics were independent of the dose in the range used here. Thus, most of poloxamer 108 was eliminated rapidly in rats by renal excretion, and a smaller portion probably was removed by biliary excretion. These results will be applied to continuing studies of Poloxamer 108 disposition in man.

Age Factors↗
PubMed2026

Molecular Mobility of N-Acetylgalactosamine-Modified Cyclodextrins on a Polyrotaxane for Highly Efficient Liver Targeting of Antibody Chimeras and Genome-Editing Ribonucleoproteins.

Triantennary N-acetylgalactosamine (triGalNAc), which interacts strongly with the trimeric structure of asialoglycoprotein receptors (ASGPRs), is a validated platform for liver targeting. However, the intricate design and synthesis of its linkers impose high production costs and significant technical challenges. In this study, we report an alternative strategy for targeting ASGPR using monovalent GalNAc (monoGalNAc) conjugated to the cyclic molecules of polyrotaxane, which can rotate and translocate along the axial polymer chain. The intracellular uptake efficacy of monoGalNAc-modified polyrotaxane is comparable to that of triGalNAc-modified polyrotaxane and significantly higher than that of triGalNAc- or monoGalNAc-modified immobile control polymers. These results suggest that the inherent mobility of polyrotaxanes allows monoGalNAc moieties to cluster in a trivalent-like manner, thereby enhancing multivalent interactions with multiple ASGPR oligomers. The successful application of monoGalNAc-modified polyrotaxane to lysosome-targeting antibody chimeras and genome-editing nanoparticles demonstrates that this facile technology is a highly promising alternative to conventional triGalNAc.

Rotaxanes↗