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.

Chitosan iron(III) reduces phosphorus levels in alloxan diabetes-induced rats with signs of renal failure development.

This study evaluates the effect of complex cross-linked chitosan iron-(III) (CH-FeCL) polymer as phosphate binder in renal failure induced by alloxan (150 mg/kg, i.p.) in rats. The animals (male and female) were divided into four groups and received the treatment once a day for 15 days: (i) control group, which received a single injection of saline (3 ml/kg, i.p.) and normal diet; (ii) alloxan group, which received only a dose of alloxan and normal diet; (iii) phosphate (PO4) group, which received diet supplemented with phosphate 1.2%; and (iv) CH-FeCL group, which received diet supplemented with phosphate 1.2% + CH-FeCL 0.5% (0.054% Fe elemental). It was observed that the CH-FeCL treatment did not alter body-weight, relative weight of the organs and haematological parameters in the treated and control groups for both sexes. However, a decrease in serum phosphorus level of the CH-FeCL group was observed after 15 days, compared with the phosphate group in both sexes. The serum iron concentration of the CH-FeCL group did not differ from the control group in either sex. CH-FeCL polymer decreases intestinal phosphate absorption in rats with renal failure and is promising for the treatment of phosphate retention in patients with renal failure.