The fate of poly(vinyl alcohol) (PVA) of weight average molar mass of 125,000 g/mol after administration into the peritoneum of rabbits has bean studied by various methods. PVA was spin-labeled with a nitroxide radical and then detected in urine using electron spin resonance (ESR) spectroscopy. Furthermore, unlabeled polymer was also administered to rabbits, then the urine was collected, dialyzed, precipitated, and the excretion of PVA was confirmed by size exclusion chromatography (SEC), FTIR spectroscopy, and (1)H NMR spectroscopy. ESR and SEC results show that, despite its relatively high molar mass, PVA is excreted through the kidneys without significant molar mass changes. Nevertheless, NMR and FTIR spectra show slight differences between the excreted and neat PVA. Possible causes of these discrepancies are discussed.
Block copolymers are able to reverse multidrug resistance (MDR) of tumor cells by a yet unknown mechanism. The drug efflux system's direct and indirect inhibition mediated by polymer P-glycoprotein (Pgp) interactions or adenosine triphosphate (ATP) depletion, respectively, may be involved in MDR reversal as well as damage to the membrane barrier caused by polymer insertion into the membrane. To test the latter hypothesis, cellular drug accumulation was monitored in the presence of both overexpressed fluorescently labeled Pgp and different block copolymers. Therefore, a new triblock copolymer (poly(ethylene oxide)- block-poly(hexafluoropropylene oxide)- block-poly(ethylene oxide)) was designed and synthesized by combined polymerization and polymer analogous reaction. Its administration induced drug uptake, whereas control cells with high Pgp expression levels showed no drug accumulation. Drug uptake was even more pronounced in the presence of another triblock copolymer: (poly(perfluorohexylethyl methacrylate)- block-poly(ethylene oxide)- block-poly(perfluorohexylethyl methacrylate). The latter polymer's lack of ionophoric activity suggests that ion transport facilitation by polymers is not a determinative factor for MDR reversal.
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