Nanoscale Delivery of Resveratrol towards Enhancement of Supplements and Nutraceuticals

Abstract

Resveratrol was investigated in terms of its stability, biocompatibility and intestinal permeability across Caco-2 cell monolayers in its free form or encapsulated in solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). SLNs and NLCs presented a mean diameter between 160 and 190 nm, high negative zeta potential of -30 mV and resveratrol entrapment efficiency of 80%, suggesting they are suitable for resveratrol oral delivery. Nanoencapsulation effectively protected resveratrol from photodegradation, and MTT assays demonstrated that neither resveratrol nor lipid nanoparticles adversely affected cell viability and integrity of Caco-2 cell monolayers. The in vitro intestinal permeability of resveratrol was significantly increased by NLCs, and SLNs did not impair the absorption of resveratrol. Resveratrol oral absorption can be enhanced during meals, since the intestinal permeability was increased in the presence of fed-state intestinal juices. SLNs and NLCs constitute carrier systems for resveratrol oral administration, for further use as supplements or nutraceuticals.

Keywords: biocompatibility; intestinal permeability; lipid nanoparticles; nanodelivery systems; oral bioavailability; resveratrol.

Figure 1

Photostability study of trans-resveratrol exposed to 312 nm UV light for four hours. (A) free resveratrol; (B) resveratrol loaded in SLNs; (C) resveratrol loaded in NLCs; (D) Photodegradation profile of trans-resveratrol in aqueous solution (■) compared to the compound encapsulated in SLNs (∆) and NLCs (○).

Figure 2

Caco-2 cell viability assessed by MTT assay after 4 h of incubation with increasing concentrations of samples. (A) Placebo SLNs (▨) and placebo NLCs (□) formulations; (B) free resveratrol (■) and resveratrol-loaded SLNs (▨) or NLCs (□). Note: All values represent the mean ± standard deviation (n = 3). Results were analyzed and compared with a DMEM medium, which represents the maximum of cell viability. (*) denotes statistically significant differences (p < 0.05) from DMEM.

Figure 3

Unstained photographs of Caco-2 cells. (A) Immediately after seeding and (B) with 100% of confluence. Magnification: 100×.

Figure 4

Resveratrol permeability over 4 hours of cumulative transport across Caco-2 cell monolayer mimicking intestinal permeability conditions, on free-form (■) and encapsulated in SLNs (∆) or NLCs (○) in 3 different transport media. (A) HBSS; (B) FaSSIF and (C) FeSSIF. Note: All values represent the mean ± standard deviation (n = 3). Results were analyzed and compared with the free form of resveratrol. (*) denotes statistically significant differences (p < 0.05).