Docosahexaenoic acid nanoencapsulated with anti-PECAM-1 as co-therapy for atherosclerosis regression.

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.

The use of factorial design to evaluate the oxidation of oils containing different types of omega-3 fatty acids.

BACKGROUND: Omega-3 fatty acids (n3 FA) promote beneficial effects on cardiovascular diseases, but they are highly susceptible to oxidation, which leads to the formation of potentially toxic secondary products. In this study, the antioxidant capacity of natural compounds (sinapic acid and rutin) was evaluated using an accelerated model to oxidize the oils. Five inducers (temperature, Fe2+ , 2,2'-azobis(2-amidinopropane) dihydrochloride, ascorbyl palmitate and the hydrophobic 2,2'-azobis-2,4-dimethylvaleronitrile (AMVN)) were combined in a factorial design to accelerate the oxidation of three oils (flaxseed, echium and fish) containing different sources of n3 FA. RESULTS: Lipid hydroperoxide (LOOH) and thiobarbituric acid reactive substance (TBARS) concentrations estimated using the regression models did not differ from the observed values. AMVN + Fe2+ increased TBARS in all samples. CONCLUSION: The values for the oxidative markers obtained 48 h after induction were similar to those obtained when the oils were heated at 60 ° C for 15 days. Of a number of volatile compounds formed from the oxidation of different n3 FA sources, (E,E)-2,4-heptadienal, (E,E)-2,4-decadienal, decanal, undecanal and (E)-2-undecenal were identified in all samples and could be used as more specific oxidative markers. Using the accelerated model, rutin improved the oxidative stability of fish oil, probably due to the presence of a catechol group in its chemical structure. © 2017 Society of Chemical Industry.