1.
Docosahexaenoic acid nanoencapsulated with anti-PECAM-1 as co-therapy for atherosclerosis regression.
de Castro Leão, M, Raffin Pohlmann, A, de Cristo Soares Alves, A, Helena Poliselli Farsky, S, Klimuk Uchiyama, M, Araki, K, Sandri, S, Stanisçuaski Guterres, S, Alves Castro, I
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 2021;:99-107
Abstract
Atherosclerosis is a non-resolving inflammatory condition that underlies major cardiovascular diseases.Recent clinical trial using an anti-inflammatory drug has showna reduction of cardiovascular mortality, but increased the susceptibility to infections. For this reason, tissue target anti-inflammatory therapies can represent a better option to regress atherosclerotic plaques. Docosahexaenoic acid (DHA) is a natural omega 3 fatty acidcomponentof algae oil and acts asaprecursor of several anti-inflammatory compounds, such the specialized proresolving lipid mediators(SPMs). During the atherosclerosis process, the inflammatory condition of the endothelium leads to the higher expression of adhesion molecules, such as Endothelial Cell Adhesion Molecule Plate 1 (PECAM-1 or CD31), as part of the innate immune response. Thus, the objective of this study was to develop lipid-core nanocapsules with DHA constituting the nucleus and anti-PECAM-1 on their surface and drive this structure to the inflamed endothelium. Nanocapsules were prepared by interfacial deposition of pre-formed polymer method. Zinc-II was added to bind anti-PECAM-1 to the nanocapsule surface by forming an organometallic complex. Swelling experiment showed that the algae oil act as non-solvent for the polymer (weight constant weight for 60 days, p > 0.428) indicating an adequate material to produce kinetically stable lipid-core nanocapsules (LNC). Five formulations were synthesized: Lipid-core nanocapsules containing DHA (LNC-DHA) or containing Medium-chain triglycerides (LNC-MCT), multi-wall nanocapsules containing DHA (MLNC-DHA) or containing MCT (MLNC-MCT) and the surface-functionalized (anti-PECAM-1) metal-complex multi-wall nanocapsules containing DHA (MCMN-DHA-a1). All formulations showed homogeneous macroscopic aspects without aggregation. The mean size of the nanocapsules measured by laser diffraction did not show difference among the samples (p = 0.241). Multi-wall nanocapsules (MLNC) showed a slight increase in the mean diameter and polydispersity index (PDI) measured by DLS, lower pH and an inversion in the zeta-potential (ξP) compared to LNCs. Conjugation test for anti-PECAM-1 showed 94.80% of efficiency. The mean diameter of the formulation had slightly increased from 160 nm (LCN-DHA) and 162 nm (MLNC-DHA) to 164 nm (MCMN-DHA-a1) indicating that the surface functionalization did not induce aggregation of the nanocapsules. Biological assays showed that the MCMN-DHA-a1 were uptaken by the HUVEC cells and did not decrease their viability. The surface-functionalized (anti- PECAM-1) metal-complex multi-wall nanocapsules containing DHA (MCMN-DHA-a1) can be considered adequate for pharmaceutical approaches.
2.
Higher-Dose DHA Supplementation Modulates Immune Responses in Pregnancy and Is Associated with Decreased Preterm Birth.
Valentine, CJ, Khan, AQ, Brown, AR, Sands, SA, Defranco, EA, Gajewski, BJ, Carlson, SE, Reber, KM, Rogers, LK
Nutrients. 2021;(12)
Abstract
Pregnancy and parturition involve extensive changes in the maternal immune system. In our randomized, multi-site, double-blind superiority trial using a Bayesian adaptive design, we demonstrated that 1000 mg/day of docosahexaenoic acid (DHA) was superior to 200 mg/day in preventing both early preterm birth (less than 34 weeks' gestation) and preterm birth (less than 37 weeks' gestation). The goal of this secondary study is to compare the effects of 1000 mg/day versus 200 mg/day on maternal inflammation, a possible mechanism by which DHA may prevent preterm birth. Maternal blood samples were collected at enrollment (12-20 weeks' gestation) and at delivery. Red blood cell DHA levels were measured by gas chromatography, and plasma concentrations of sRAGE, IL-6, IL-1β, TNFα, and INFγ were measured by ELISA. Data were analyzed for associations with the DHA dose, gestational age at birth, and preterm birth (<37 weeks). Higher baseline and lower delivery levels of maternal sRAGE were associated with a greater probability of longer gestation and delivery at term gestation. Higher-dose DHA supplementation increased the probability of a smaller decrease in delivery sRAGE levels. Higher IL-6 concentrations at delivery were associated with the probability of delivering after 37 weeks, and higher-dose DHA supplementation increased the probability of greater increases in IL-6 concentrations between enrollment and delivery. These data provide a proposed mechanistic explanation of how a higher dose of DHA during pregnancy provides immunomodulatory regulation in the initiation of parturition by influencing sRAGE and IL-6 levels, which may explain its ability to reduce the risk of preterm birth.
3.
Marine omega-3 fatty acid supplementation in non-alcoholic fatty liver disease: Plasma proteomics in the randomized WELCOME* trial.
Manousopoulou, A, Scorletti, E, Smith, DE, Teng, J, Fotopoulos, M, Roumeliotis, TI, Clough, GF, Calder, PC, Byrne, CD, Garbis, SD
Clinical nutrition (Edinburgh, Scotland). 2019;(4):1952-1955
Abstract
BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) is a liver condition characterised by liver fat accumulation and often considered to be the liver manifestation of metabolic syndrome. The aim of this study was to examine in patients with NAFLD the system-wide effects of treatment with docosahexaenoic acid + eicosapentaenoic acid (DHA + EPA) versus placebo on the plasma proteome. METHODS Plasma from patients that participated in a 15-18 months randomised, double-blind placebo-controlled trial testing the effects of 4 g DHA + EPA daily was analysed using depletion-free quantitative proteomics. RESULTS Bioinformatics interpretation of the proteomic analysis showed that DHA + EPA treatment affected pathways involving blood coagulation, immune/inflammatory response and cholesterol metabolism (p < 0.05). Two key proteins of cardiovascular risk, prothrombin and apolipoprotein B-100, were shown to decrease as a result of DHA + EPA supplementation [Prothrombin: Males DHA + EPA Mean iTRAQ log2ratio (SD) = -0.13 (0.20) p = 0.05, Females DHA + EPA Mean iTRAQ log2ratio (SD) = -0.48 (0.35) p = 0.03; Apo B-100: Males DHA + EPA Mean iTRAQ log2ratio (SD) = -0.24 (0.16) p = 0.01, Females DHA + EPA Mean iTRAQ log2ratio (SD) = -0.15 (0.05) p = 0.02]. CONCLUSIONS Plasma proteomics applied in a randomised, placebo-controlled trial showed that high dose DHA + EPA treatment in patients with NAFLD affects multiple pathways involved in chronic non-communicable diseases.