2019 Anti-inflammatory Surface Coatings Based on Polyelectrolyte Multilayers of Heparin and Polycationic Nanoparticles of Naproxen-Bearing Polymeric Drugs

Hala Al-Khoury, Eva Espinosa-Cano, María Rosa Aguilar, Julio San Román, Frank Syrowatka, Georg Schmidt and Thomas Groth

Biomacromolecules 2019, 20, 10, 4015-4025; DOI: 10.1021/acs.biomac.9b01098

Department Biomedical Materials, Institute of Pharmacy, Martin Luther University Halle Wittenberg, Heinrich Damerow Strasse 4, 06120 Halle (Saale), Germany

Interdisciplinary Centre of Materials Science, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany

Biomaterials Group, Department of Polymeric Nanomaterials and Biomaterials, Institute of Polymer Science and Technology, ICTP-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain

Networking Biomedical Research Centre in Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, 28029 Madrid, Spain

Interdisciplinary Centre of Applied Science, Martin Luther University Halle-Wittenberg, 06099 Halle (Saale), Germany


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 anti-inflammatory 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.