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

Author(s)

Leao, Matheus de Castro ^[1] ; Pohlmann, Adriana Raffin ^[2] ; Alves, Aline de Cristo Soares ^[2] ; Farsky, Sandra Helena Poliselli ^[3] ; Uchiyama, Mayara Klimuk ^[4] ; Araki, Koiti ^[4] ; Sandri, Silvana ^[3] ; Guterres, Silvia Staniscuaski ^[5] ; Castro, Inar Alves ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Food & Expt Nutr, LADAF, Av Lineu Prestes 580, B14, BR-05508900 Sao Paulo - Brazil

^[2] Univ Fed Rio Grande do Sul, Inst Chem, Dept Organ Chem, Porto Alegre, RS - Brazil

^[3] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Porto Alegre, RS - Brazil

^[4] Univ Sao Paulo, Inst Chem, Dept Fundamental Chem, Sao Paulo - Brazil

^[5] Univ Fed Rio Grande do Sul, Pharmaceut Fac, Dept Prod & Drugs Control, Porto Alegre, RS - Brazil

• Document type: Journal article
• Source: EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS; v. 159, p. 99-107, FEB 2021.
• Web of Science Citations: 0

Abstract

Atherosclerosis is a non-resolving inflammatory condition that underlies major cardiovascular diseases. Recent clinical trial using an anti-inflammatory drug has shown a 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 acid - component of algae oil and acts as a precursor 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 (xi P) 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 nano-capsules. 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. (AU)

• FAPESP's process: 19/21029-3 - Docosahexaenoic acid nanoencapsulated with anti-Pecam-1 as strategy to increase atherosclerotic plaque stability
• Grantee: Inar Castro Erger
• Support Opportunities: Regular Research Grants