Fabrication of Biodegradable Poly(naringin) Particles with Antioxidant Activity and Low Toxicity

Naringin (NR, 4', 5,7 trihydrocyflavanone-7-O-rhamnoglucoside) is a flavanone found in citrus fruit that is composed of a phenolic compound, naringenin, and a disaccharide, neohesperidose. Poly(NR) [p(NR)] particles in the size range of few micrometers to few hundred nanometers were prepared from highly purified NR and subsequently characterized using UV/visible spectroscopy, Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, scanning electron microscopy, thermogravimetric analysis, and zeta potential measurements. The hydrolytic degradation of p(NR) particles at 37.5 degrees C was investigated at pHs 5.4, 7.4, and 9.0. The particles degraded most rapidly at pH 7.4, with >90% degradation after 5 h. The cytotoxicity was assessed by growing COS-1 fibroblasts for 5 days in the presence of increasing concentrations of NR or eluates from the p(NR) particles. Both NR and p(NR) particles were nontoxic for these mammalian fibroblasts; at the highest concentration tested (571 mu g/mL), the percentages of surviving cells after 5 days in culture were 96.7 +/- 0.93 and 91 +/- 11% for NR and p(NR), respectively. The effect of p(NR) on red blood cell hemolysis was also negligible (<2%) at concentrations up to 100 mu g/mL; unpolymerized NR showed slightly higher levels of hemolysis than the p(NR) particles, but values never exceeded 5% at 50 and 100 mu g/mL. Both NR and p(NR) stimulated blood coagulation in a dose-dependent manner; the hemostatic effect was greater for p(NR), which, at 100 mu g/mL, stimulated in vitro blood clotting by similar to 50%. Neither NR nor eluates from p(NR) particles inhibited alpha-glucosidase activity; in fact, both provided a modest (10-30%) stimulation at concentrations from 0.67 to 1.67 mg/mL. p(NR) particles are easily synthesized, break down readily at physiological pH, and have excellent blood and biocompatibility. As such, they will be a useful carrier for drug delivery and as an oral antioxidant supplement.