Resveratrol-loaded biopolymer core–shell nanoparticles: bioavailability and anti-inflammatory effects†
The cellular uptake and simulated intestinal wall transportation of resveratrol-loaded zein/pectin nanoparticles were assessed using Caco-2 cells and monolayers, respectively. The oral bioavailabilities of encapsulated (En-RES) and free (RES) resveratrol were evaluated by monitoring the resveratrol concentration in rat plasma after oral administration. The impact of encapsulation on the anti-inflammatory activity of the resveratrol was determined using lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. The cellular uptake of encapsulated resveratrol increased appreciably with observation time (1–4 h), reaching a maximum value (≈1.06 μg mL−1) after 2 h, whereas that of free resveratrol (in DMSO) only increased slightly, reaching 0.62 μg mL−1 after 4 h. The transmembrane transport of En-RES was significantly higher than that of RES (p < 0.05): the resveratrol concentration in the receiving compartment of Costar trans-wells was 4.7-fold higher for the encapsulated resveratrol. The resveratrol concentration in the plasma of rats was measured after they were fed formulations containing a resveratrol equivalent of 20 mg per kg bodyweight. The plasma level reached a maximum value of 1.35 ± 0.26 μg mL−1 at 4 h after feeding the En-RES formulation, and then decreased to 0.19 ± 0.04 μg mL−1 after 48 h. Conversely, the plasma level only reached a maximum value of 0.31 ± 0.05 μg mL−1 at 0.5 h after feeding the free resveratrol formulation (an aqueous PEG 400 solution), and was totally cleared after 8 h. Cell culture studies suggested that En-RES exhibited a strong anti-inflammatory activity by inhibiting the production of NO, PGE2, IL-1β, IL-6, TNF-α, promoting IL-10 release, inhibiting expression of TLR4, and inhibiting phosphorylation of JNK, ERK1/2, p38 and MAPK. Overall, this research suggests that zein-pectin core/shell nanoparticles are a highly effective delivery system for resveratrol, significantly increasing its bioavailability and anti-inflammation activity. These oral delivery systems may be particularly suitable for applications in functional foods or pharmaceuticals.