Design and Investigation of New Water-Soluble Forms of α-Tocopherol with Antioxidant and Antiglycation Activity Using Amphiphilic Copolymers of N-Vinylpyrrolidone

Abstract

Water-soluble forms of α-tocopherol (TP) as an effective antioxidant were obtained by encapsulating it into nanoparticles (NPs) of amphiphilic copolymers of N-vinylpyrrolidone with triethylene glycol dimethacrylate (CPL1-TP) and N-vinylpyrrolidone with hexyl methacrylate and triethylene glycol dimethacrylate (CPL2-TP) synthesized by radical copolymerization in toluene. The hydrodynamic radii of NPs loaded with TP (3.7 wt% per copolymers) were typically ca. 50 or 80 nm depending on copolymer composition, media, and temperature. Characterization of NPs was accomplished by transmission electron microscopy (TEM), IR-, and 1H NMR spectroscopy. Quantum chemical modeling showed that TP molecules are capable to form hydrogen bonds with donor groups of the copolymer units. High antioxidant activity of both obtained forms of TP has been found by the thiobarbituric acid reactive species and chemiluminescence assays. CPL1-TP and CPL2-TP effectively inhibited the process of spontaneous lipid peroxidation as well as α-tocopherol itself. The IC50 values of luminol chemiluminescence inhibition were determined. Antiglycation activity against vesperlysine and pentosidine-like AGEs of TP water-soluble forms was shown. The developed NPs of TP are promising as materials with antioxidant and antiglycation activity and can be used in various biomedical applications.

Macromolecular Design and Engineering of New Amphiphilic N-Vinylpyrrolidone Terpolymers for Biomedical Applications

“…The existence of such regions is also proved by diffraction patterns. In the FB12 terpolymer, there are circular formations about 0.2 microns in size (Figure 10d), which are similar to those observed in the unfiltered FB7 sample [39].…”

“…However, the absorption band has a more complex shape in the TP-PVP spectrum, which may be due to the free and bound form of tocopherol in this polymer. To prove the efficiency of TP encapsulation in terpolymers, we analyzed the absorption spectra of water solutions and compared them with control experiments performed in the absence of a terpolymer, as in [39]. The absorption spectrum of the solution in the control experiment (without terpolymer) has no typical TP band at 280-300 nm.…”

“…Using the TP calibration dependency and the concentration dependency of TP-NPs in ethanol, we confirmed the full encapsulation of the compound in NPs. TP molecules can be physically entrapped with the NPs and localized in the polar shell, forming, according to quantum chemical modeling [39], the hydrogen bond to the oxygen atom of the lactam ring of the VP units. In addition, interactions of the oxygen atoms of both ether and ester groups of TEGDM and HMA units of low polar moieties of polymer chains with TP can occur.…”

“…We used the radical polymerization in solution in the presence of 1-decanthiole as traditional CTA [32] or without it [33][34][35][36][37][38][39] to produce amphiphilic VP-dimethacrylate copolymers of various compositions, molecular weights, and architectures at high yields within 2-3 h. Their molecular weight distribution (MWD) and compositional heterogeneity may be improved by fractionation. A controlled radical polymerization technique, such as RAFT, is more effective for the synthesis of a compositionally homogeneous copolymer with a narrow MWD.…”

“…In work [39], we have prepared water-soluble forms of D-α-tocopherol (TP) (Figure 1a) as an effective antioxidant by encapsulating into the nanoparticles (NPs) of an amphiphilic copolymer of N-vinylpyrrolidone with triethylene glycol dimethacrylate and amphiphilic terpolymer of N-vinylpyrrolidone with hexyl methacrylate and triethylene glycol dimethacrylate, and their high antioxidant activity has been established by the thiobarbituric acid reactive species (TBARS) and chemiluminescence assays. They effectively inhibited the process of spontaneous lipid peroxidation as well as initial TP and exhibited antiglycation activity [41] against vesperlysine and pentosidine-like AGEs.…”