Fig 1.
Synthesis of (A) resveratrol-PEG ester conjugates, (B) MeO-PEG-PLAO-Succ-RSV conjugates and (C) resveratrol-PEG ether conjugates.
Fig 2.
The down field region of 1H NMR spectra (400 MHz) for: (a) a solution of the MeO-PEGN-Succ-RSV (2 kDa) conjugate mixture in d6-DMSO; (b) a solution of resveratrol in d6-DMSO; and (c) the solution from (a) after treatment with water and heat (90°C) for ca. 1 week).
In (c) the signals for free resveratrol are highlighted in red and those for the remaining resveratrol-PEG conjugates are highlighted in blue. Full width versions of these spectra are provided in S1 File, along with a comparison with the MeO-PEG-Succ-OH starting material.
Table 1.
Physicochemical properties and stability data of Resveratrol-polymer conjugates.
Fig 3.
Determination of CMC for MeO-PEG-PLAO-Succ-RSV 2kDa.
A: plot of log (Concentration mg/L) vs Absorbance for dimethyl yellow at 441. B: plot of log (Concentration mg/L) vs Absorption maximum (nm) for dimethyl yellow. Mw quoted is for polymer only. Mw for RSV is 228 Da.
Table 2.
Polymeric micelle size and polydispersibility index of resveratrol-polymer conjugates.
Fig 4.
DPPH inhibition profile of A: Resveratrol; B: MeO-PEGN-Succ-RSV, 2kDa; C: MeO-PEG-RSV ether, 2kDa All the data are presented as mean ± SD (n = 3).
Mw quoted is for polymer only. Mw for RSV is 228 Da.
Fig 5.
The degradation profile of A: Resveratrol and B: MeO-PEG-PLAO-Succ-RSV 2 kDa in microsomal incubations with UDPA.
C: MeO-PEGN-Succ-RSV 2 kDa in microsomal incubation, D: MeO-PEGN-Succ-RSV 2 kDa in incubation buffer without microsomes. E: MeO-PEG-RSV ether 2 kDa in microsomal incubation. Mw quoted is for polymer only. Mw for RSV is 228 Da.
Fig 6.
Chromatogram of resveratrol in microsomal incubations at 10 minutes.
Fig 7.
Plasma concentration-time profiles for resveratrol formulations in rats.
Doses are resveratrol equivalents and data are mean ± SD. Symbols:MeO-PEG-RSV ether 2 kDa, 2 mg/kg (●; n = 5); MeO-PEG-RSV ether 5 kDa, 2 mg/kg (◯; n = 6); MeO-PEG-PLAO-Succ-RSV 2kDa, 2 mg/kg (▲; n = 6); Resveratrol, 10 mg/kg (▽; n = 4).
Table 3.
Pharmacokinetic parameters for resveratrol and its conjugate formulations in rats.