Nano-anisotropic surface coating based on drug immobilized pendant polymer to suppress macrophage adhesion response.
Exploring drug molecules for material design, to harness concepts of nano-anisotropy and ligand-receptor interactions, are rather elusive. The aim of this study is to demonstrate the bottom-up design of a single-step and bio-interactive polymeric surface coating, based on drug based pendant polymer. This can be applied on to polystyrene (PS) substrates, to suppress macrophage adhesion and spreading. The drug molecule is used in this coating for two purposes. The first one is drug as a "pendant" group, to produce nano-anisotropic properties that can enable adhesion of the coatings to the substrate. The second purpose is to use the drug as a "ligand", to produce ligand-receptor interaction, between the bound ligand and receptors of albumin, to develop a self-albumin coat over the surface, by the preferential binding of albumin in biological environment, to reduce macrophage adhesion. Our in silico studies show that, diclofenac (DIC) is an ideal drug based "ligand" for albumin. This can also act as a "pendant" group with planar aryl groups. The combination of these two factors can help to harness, both nano-anisotropic properties and biological functions to the polymeric coating. Further, the drug, diclofenac (DIC) is immobilized to the polyvinyl alcohol (PVA), to develop the pendant polymer (PVA-DIC). The interaction of bound DIC with the albumin is a ligand-receptor based interaction, as per the studies by circular dichroism, differential scanning calorimetry, and SDS-PAGE. The non-polar π-π* interactions are regulating; the interactions between PVA bound DIC-DIC interactions, leading to "nano-anisotropic condensation" to form distinct "nano-anisotropic segments" inside the polymeric coating. This is evident from, the thermo-responsiveness and uniform size of nanoparticles, as well as regular roughness in the surface coating, with similar properties as that of nanoparticles. In addition, the hydrophobic DIC-polystyrene (PS) interactions, between the PVA-DIC coating and PS-substrate produce improved coating stability. Subsequently, the PVA-DIC coated substrate has the maximum capacity to suppress the macrophage (RAW 264.7 cell line) adhesion and spreading, which is partly due to wavy-surface topography of hydrophilic PVA and preferential albumin binding capacity of PVA bound DIC. Our result shows that, such surfaces suppress the macrophages, even under stimulation with lipopolysaccharide (LPS). The modified tissue culture plates can be used as an in vitro tool, to study the macrophage response under low spatial cues.
Biosurface Technology Division (nFADDS), Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Science and Technology, Poojappura, Thiruvananthapuram, Kerala, India.
K
K
Kaladhar
Institute for Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Philipps-University Marburg, Marburg, Germany. Electronic address: renzh@med.uni-marburg.de.
H
H
Renz
Biosurface Technology Division (nFADDS), Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Science and Technology, Poojappura, Thiruvananthapuram, Kerala, India. Electronic address: sharmacp@sctimst.ac.in.
C P
CP
Sharma
D000418:Albumins / Q000737:chemistry*; D000818:Animals; D016880:Anisotropy; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D004008:Diclofenac / Q000737:chemistry*; D004337:Drug Carriers; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D051379:Mice; D062105:Molecular Docking Simulation; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011108:Polymers / Q000138:chemical synthesis / Q000494:pharmacology*; D011137:Polystyrenes / Q000737:chemistry; D011142:Polyvinyl Alcohol / Q000737:chemistry; D013816:Thermodynamics
D000418:Albumins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D008070:Lipopolysaccharides; D011108:Polymers; D011137:Polystyrenes; D004008:Diclofenac; D011142:Polyvinyl Alcohol
Biotechnology; Blood compatibility; Colloids; Nanoparticle; Surface modification