New miceller agent for antioxidation therapy based on XO inhibition using AHPP

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We had previously discovered that AHPP exhibited a potent inhibitory effect against xanthine oxidase (XO). The difficulty to make AHPP as pharmaceutical agent resides in poor water solubility and low MW that has short in vivo t1/2 and no targeting capacity to the diseased site.To solve these problems we synthesized PEG-conjugate of AHPP and SMA (styrene-co-maleic acid) micelles containing AHPP. As the results, we found (1) XO inhibitory activity in vitro of both polymeric AHPP showed about 80% of that of free AHPP, and satisfactory. (2) In vivo evaluation of ischemia-reperfusion (I/R) model of liver, the polymeric AHPP showed significant effect preventing I/R induced tissue (liver) toxicity. (3) Oral administration of PEG-AHPP in lipid formation in the spontaneously hypertensive rats resulted in lowering of blood pressure to normal range. (4) The antihypertensive effect lasted even more than 24 hr after one oral administration.