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 °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 μg/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 μg/mL; unpolymerized NR showed slightly higher levels
of hemolysis than the p(NR) particles, but values never exceeded 5%
at 50 and 100 μg/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 μg/mL, stimulated in vitro blood clotting
by ∼50%. Neither NR nor eluates from p(NR) particles inhibited
α-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.