Astaxanthin nanoparticles with improved chemical stability, oral bioavailability, and hepatoprotective effects

抄録

[Purpose] The present study was aimed to develop stabilized astaxanthin (AX) nanoparticles (sNP/AX) to improve the physicochemical properties, oral bioavailability, and hepatoprotective effects of AX.[Methods] sNP/AX were prepared by flash nanoprecipitation technique using a multi-inlet vortex mixer. To prevent the oxidative degradation of AX during the preparation and storage of sNP/AX, vitamin E and C were used as co-stabilizing agents with poloxamer 407 in the formation of sNP/AX. The physicochemical properties and pharmacokinetic behavior of sNP/AX in rats were evaluated. The hepatoprotective effects of orally-taken sNP/AX were evaluated in a rat model of acute liver injury.[Results] AX content in sNP/AX without anti-oxidative additives was significantly reduced to 11% even at 4°C of storage condition. On the other hand, vitamin C in the aqueous phase significantly stabilized the AX during the preparation process, and vitamin E in sNP/AX markedly improved the storage stability of sNP/AX, as evidenced by remaining AX contents of ca. 92 and 75% after 4 weeks of storage at 4°C and 25°C, respectively. The mean particle size of developed sNP/AX was 215 nm with a polydispersity index of 0.3. The release properties of AX from sNP/AX were significantly higher compared with crystalline AX in pH 6.8 media, and orally-dosage of sNP/AX (33.2 mg-AX/kg) to rats exhibited improved systemic exposure of AX, whereas the oral absorption of AX in crystalline AX group was negligible. In a rat model of acute liver injury, pretreatment with sNP/AX (33.2 mg AX/kg, p.o.) led to marked attenuation of hepatic damage on the basis of histological observation and decreased levels of plasma biomarkers of alanine aminotransferase and aspartate aminotransferase by 62% and 51%, respectively.[Conclusion] The strategic application of anti-oxidative additives to sNP/AX could have a potential impact on the improvement of physicochemical properties and oral bioavailability of AX.