Anti-inflammatory Surface Coatings Based on Polyelectrolyte Multilayers of Heparin and Polycationic Nanoparticles of Naproxen-Bearing Polymeric Drugs

Abstract

Immune response to biomaterials can produce chronic inflammation and fibrosis leading to implant failure, which is related to the surface properties of the biomaterials. This work describes the preparation and characterization of polyelectrolyte multilayer (PEM) coatings that combine the anti-inflammatory activity of heparin as polyanion with the potential release of Naproxen, a nonsteroidal anti-inflammatory drug from polymeric nanoparticles (NP) with cationic surface charge. The polyelectrolyte multilayers were characterized by physical methods to estimate multilayer growth, thickness, zeta potential, and topography. It was found that multilayers with NP had negative zeta potentials and expressed a viscoelastic behavior, while studies of topography showed that nanoparticles formed continuous surface coatings. THP-1-derived macrophages were used to study short-term antiinflammatory activity (time scale 48 h), showing that PEM that contained heparin reduced cell adhesion and IL1-β secretion, when compared to those with polystyrenesulfonate, used as alternative polyanion in multilayer formation. On the other hand, the presence of NP in PEM was related to a reduced foreign body giant cell formation after 15 days, when compared to PEM that contained chitosan as alternative polycation, which suggests a long-term anti-inflammatory effect of Naproxen-containing nanoparticles. It was also shown that macrophages were able to take up NP from multilayers, which indicates a release of Naproxen by digestion of NP in the lysosomal compartment. These findings indicate that surface coatings composed of heparin and Naproxen-based NP on implants such as biosensors have the potential to attenuate foreign body reaction after implantation, which may improve the long-term functionality of implants.

Engineering osteogenic microenvironments by combination of multilayers from collagen type I and chondroitin sulfate with novel cationic liposomes

“…The average ζ potential of liposomes was 49.5 4.8 mV. This result indicates a highly positive charged surface, useful as a polycationic component for multilayer formation, as it was shown previously by our group using cationic polymeric particles with a ζ potential of ≈30 mV [ 38 ]. A further advantage is that the positive charge also provides colloidal stability in suspension [ 39 ].…”

Anti-Inflammatory Polymeric Nanoparticles Based on Ketoprofen and Dexamethasone

“…The methacrylic derivative of ketoprofen (HKT) ( Figure 1 a) was synthesized via esterification reaction as previously described for its homologous based on ibuprofen and naproxen [ 24 , 25 ]. Briefly, KT (TCI, 1 equiv) was dissolved in dichloromethane (DCM, Aldrich, St. Louis, MO, USA).…”

Layer-By-Layer Assemblies of Biopolymers: Build-Up, Mechanical Stability and Molecular Dynamics

“…Natural polyelectrolytes, such as components of the extracellular matrix (hyaluronate, collagen, elastin, fibronectin, laminin), proteins (protamine, gelatin), nucleic acids (DNA and RNA) and polysaccharides (which are the most abundant family of natural polymers), have also gained considerable attention as the building blocks for the multilayers [ 24 ]. PEMs fabricated from such biogenic polyelectrolytes hold specific bioactivities (e.g., ant-inflammatory [ 25 , 26 ] and osteogenic activities [ 27 ]) that are useful for a variety of bioapplications. In some studies, self-assembled structures such as liposomes and micelles were also used as the building blocks for LbL deposition [ 28 , 29 ].…”