Effect of nanocapsules containing docosahexaenoic acid in mice with chronic inflammation

Matheus de Castro Leão; Isabella di Piazza; Sarah Jorge Caria; Milena Fronza Broering; Sandra Helena Poliselli Farsky; Mayara Klimuk Uchiyama; Koiti Araki; Kennedy Bonjour; Bruno Cogliati; Adriana Raffin Pohlmann; Silvia Stanisçuaski Guterres; Inar Alves Castro

doi:10.1016/j.biopha.2023.115474

Effect of nanocapsules containing docosahexaenoic acid in mice with chronic inflammation

Biomed Pharmacother. 2023 Nov:167:115474. doi: 10.1016/j.biopha.2023.115474. Epub 2023 Sep 21.

Affiliations

¹ Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil.
² Department of Clinical & Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil.
³ Department of Fundamental Chemistry, Institute of Chemistry, University of São Paulo, São Paulo, São Paulo, Brazil.
⁴ Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, São Paulo, Brazil.
⁵ Department of Organic Chemistry, Institute of Chemistry, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
⁶ Department of Production and Drugs Control, Pharmaceutical Faculty, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
⁷ Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil. Electronic address: inar@usp.br.

PMID: 37741249
DOI: 10.1016/j.biopha.2023.115474

Abstract

Background: Omega 3 fatty acids, such as docosahexaenoic acid (DHA) have been widely consumed as supplements to control chronic inflammation. Nanocapsules containing DHA (MLNC-DHA-a1) were developed and showed excellent stability. Thus, our objective was to evaluate the effect of MLNC-DHA-a1 nanocapsules on biomarkers of chronic inflammation.

Methods: Cells viability was determined by flow cytometry. The uptake of MLNC-DHA-a1 nanocapsules by macrophages and their polarization were determined. In vivo, LDLr^(-,-) mice were fed a Western diet to promote chronic inflammation and were treated with MLNC-DHA-a1 nanocapsules, intravenously injected via the caudal vein once a week for 8 weeks.

Results: MLNC-DHA-a1 nanocapsules decreased the concentration of TNFα (p = 0.02) in RAW 264.7 cells compared to the non-treated group (NT), with no changes in IL-10 (p = 0.29). The nanocapsules also exhibited an increase in the M2 (F4/80⁺ CD206) phenotype (p < 0.01) in BMDM cells. In vivo, no difference in body weight was observed among the groups, suggesting that the intervention was well tolerated. However, compared to the CONT group, MLNC-DHA-a1 nanocapsules led to an increase in IL-6 (90.45 ×13.31 pg/mL), IL-1β (2.76 ×1.34 pg/mL) and IL-10 (149.88 ×2.51 pg/mL) levels in plasma.

Conclusion: MLNC-DHA-a1 nanocapsules showed the potential to promote in vitro macrophage polarization and were well-tolerated in vivo. However, they also increased systemic pro-inflammatory cytokines. Therefore, considering that this immune response presents a limitation for clinical trials, further studies are needed to identify the specific compound in MLNC-DHA-a1 that triggered the immune response. Addressing this issue is essential, as MLNC-DHA-a1 tissue target nanocapsules could contribute to reducing chronic inflammation.

Keywords: Atherosclerosis; Cytokines; DHA; Inflammation; Nanocapsules; Omega 3.