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. 2024 Jun 14:19:5995-6014.
doi: 10.2147/IJN.S464849. eCollection 2024.

Intestinal Targeted Nanogel with Broad-Spectrum Autonomous ROS Scavenging Performance for Enhancing the Bioactivity of trans- Resveratrol

Jingwen Xu  1   2 , Yue Zhang  1   2 , Xiaolin Yao  1 , Sijuan Wang  1   2 , Kaiqiang Lv  1   2 , Guangwen Luo  1   2 , Jiaqi Wang  1   2 , Guoliang Li  1
Affiliations

Intestinal Targeted Nanogel with Broad-Spectrum Autonomous ROS Scavenging Performance for Enhancing the Bioactivity of trans- Resveratrol

Jingwen Xu et al. Int J Nanomedicine. .

Abstract

Introduction: To improve the bioavailability of trans-resveratrol (trans-Res), it is commonly co-delivered with antioxidant bioactives using a complex synthetic intestinal targeted carrier, however, which makes practical application challenging.

Methods: A nanogel (Ngel), as broad-spectrum autonomous ROS scavenger, was prepared using selenized thiolated sodium alginate (TSA-Se) and crosslinked with calcium lactate (CL) for loading trans-Res to obtain Ngel@Res, which maintained spherical morphology in the upper digestive tract but broke down in the lower digestive tract, resulting in trans-Res release.

Results: Under protection of Ngel, trans-Res showed enhanced stability and broad-spectrum ROS scavenging activity. The synergistic mucoadhesion of Ngel prolonged the retention time of trans-Res in the intestine. Ngel and Ngel@Res increased the lifespan of Caenorhabditis elegans to 26.00 ± 2.17 and 26.00 ± 4.27 days by enhancing the activity of antioxidases, upregulating the expression of daf-16, sod-5 and skn-1, while downregulating the expression of daf-2 and age-1.

Conclusion: This readily available, intestinal targeted selenized alginate-based nanogel effectively improves the bioactivity of trans-Res.

Keywords: intestinal targeted delivery; mucoadhesion; seleno-alginate; synergistic antioxidant; trans-resveratrol.

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Conflict of interest statement

The authors claim that there are no conflicts to declare.

Figures

None
Graphical abstract
Figure 1
Figure 1
(A) Synthesis of TSA and TSA-Se, formation of Ngel, trans-Res loaded Ngel (Ngel@Res) and its anti-aging mechanism for C. elegans. (B) FTIR spectra of Ngel and its precursors, as well as Ngel@Res. (C) Dh of the Ngel and Ngel@Res nanogels with different compositions. (D) Zeta potentials of TSA, TSA-Se, trans-Res, Ngel-3 and Ngel-3@Res. (E) XRD patterns of trans-Res, Ngel-3 and Ngel-3@Res.
Figure 2
Figure 2
TEM photographs of (A) Ngel-3, (B) Ngel-3@Res. Ngel-3@Res digested by SGF for (C) 2 h, followed by treatment with SIF for (D) 2 h and (E) 4 h, respectively. (F) Partial enlarged view of Figure (E). EDS elemental maps of C, O, Ca, S, Se element of Ngel-3@Res (G–K) and their overlay image (L).
Figure 3
Figure 3
The influence of pH, temperature, ultraviolet radiation and redox agents on the retention rate of trans-Res with or without Ngel-3 protection during 5 h incubation. pH: (A) 2.0, (B) 5.0 and (C) 7.0; Temperature: (D) 25 °C, (E) 37 °C and (F) 60°C; Redox: (G) 1.0% H2O2, (H) 0.20% Na2SO3 and (I) ultraviolet radiation. The inset at the lower right corner of each picture presents the appearance of Ngel-3@Res (left) and trans-Res (right) after corresponding treatment.
Figure 4
Figure 4
(A) SA, TSA, TSA-Se-3 and (B) Ngel with different Se concentrations against representative free radicals including •OH, •DPPH, and •ABTS+. The representative free radical scavenging rate of the samples, including trans-Res, Ngel-3 and Ngel-3@Res before (C) and after (D) simulated gastrointestinal digestion. AsA was used as control group. The amount of mucin absorbed by trans-Res, SA-SeKGM/CL nanogel, Ngel-3 and Ngel-3@Res at pH 2.0, 5.0 and 7.0 (E). The release curves of trans-Res from Ngel-3@Res in the medium that simulates intestinal (F), gastric and intestinal (G), and gastric, duodenal and intestinal (H) microenvironments.
Figure 5
Figure 5
(A) The lifespan of C. elegans exposed to trans-Res, Ngel-3 and Ngel@Res at different concentrations. (B) The survival time of trans-Res, Ngel-3 and HC Ngel-3@Res treated C. elegans under oxidative stress. (C–F) Fluorescence images and (G) fluorescence intensity of C. elegans in (D) control group, and C. elegans treated with (D) trans-Res, (E) Ngel-3 and (F) HC Ngel-3@Res after 7 days. The activity of antioxidases such as (H) SOD, (I) CAT and (J) GSH-Px, as well as (K) the content of MDA in C. elegans incubated with trans-Res, Ngel-3 and HC Ngel-3@Res after 7 days. (L) Effect of trans-Res, Ngel-3 and HC Ngel-3@Res on gene expression levels of daf-2, age-1, daf-16, sod-5 and skn-1 in N2 nematodes by qRT-PCR. Untreated C. elegans were used as control group. *, ** and *** represent p<0.05, p<0.01 and p<0.001, respectively.
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