Biocompatible Nanocoatings of Fluorinated Polyphosphazenes through Aqueous Assembly

Abstract

Nonionic fluorinated polyphosphazenes, such as poly[bis(trifluoroethoxy)phosphazene] (PTFEP), display superb biocompatibility, yet their deposition to surfaces has been limited to solution casting from organic solvents or thermal molding. Herein, hydrophobic coatings of fluorinated polyphosphazenes are demonstrated through controlled deposition of ionic fluorinated polyphosphazenes (iFPs) from aqueous solutions using the layer-by-layer (LbL) technique. Specifically, the assemblies included poly[(carboxylatophenoxy)(trifluoroethoxy)phosphazenes] with varied content of fluorine atoms as iFPs (or poly[bis(carboxyphenoxy)phosphazene] (PCPP) as a control nonfluorinated polyphosphazene) and a variety of polycations. Hydrophobic interactions largely contributed to the formation of LbL films of iFPs with polycations, leading to linear growth and extremely low water uptake. Hydrophobicity-enhanced ionic pairing within iFP/BPEI assemblies gave rise to large-amplitude oscillations in surface wettability as a function of capping layer, which were the largest for the most fluorinated iFP, while control PCPP/polycation systems remained hydrophilic regardless of the film top layer. Neutron reflectometry (NR) studies indicated superior layering and persistence of such layering in salt solution for iFP/BPEI films as compared to control PCPP/polycation systems. Hydrophobicity of iFP-capped LbL coatings could be further enhanced by using a highly porous polyester surgical felt rather than planar substrates for film deposition. Importantly, iFP/polycation coatings displayed biocompatibility which was similar to or superior to that of solution-cast coatings of a clinically validated material (PTFEP), as demonstrated by the hemolysis of the whole blood and protein adsorption studies.

Hierarchy of Hybrid Materials—The Place of Inorganics-in-Organics in it, Their Composition and Applications

“…Its particular advantages are the flexibility to control the thickness, architecture, composition, and possibilities of incorporation of various materials (Lavalle et al, 2011) accompanied by various stimuli to control the properties (Delcea et al, 2011b). Research activities in the area of LbL include planar films (Von Klitzing, 2006; Selin et al, 2018) and capsules. In addition to nanometer-thin LbL films, so-called micrometer thick exponentially grown LbL films were developed (Lavalle et al, 2004), which can host an enormous amount of both small and high molecular weight substances due to a large thickness of multilayers, e.g., those made of biopolymers (Sustr et al, 2015, 2018; Velk et al, 2016; Vikulina et al, 2016; Prokopovic et al, 2017).…”

New Family of Water-Soluble Sulfo–Fluoro Polyphosphazenes and Their Assembly within Hemocompatible Nanocoatings

“…More details of fitting models used can be found in a previously published manuscript. 38 Salt Stability. Coatings of ∼100 nm thickness deposited on silicon wafers were exposed to 5 mL of increasing concentrations of potassium chloride in 0.01 M PB at pH 7.4 for 1 h. After exposure, samples were washed with 0.01 M PB to remove excess salt adhering to the coating and dried with nitrogen.…”

“…These results show the importance of fluorination for decreasing hemolysis, which correlates well with hemolysis studies of water-soluble components observed earlier in this study (Figure 2E) as well as with our previously published report on LbL with PPzs containing fluorinated and carboxylic groups. 23 Moreover, these PPzs demonstrate excellent biocompatibility for both LbL films and their macromolecular components in environments containing blood.…”

Main-Chain Phosphorus-Containing Polymers for Therapeutic Applications

“…The amassed data suggest both antithrombotic and superior healing characteristics for PPz coated stents, which is thought to be due to its ability to bind albumin, forming a "biomimetic" layer, which results in superior anti-inflammatory and thromboresistant properties compared to uncoated stents and indeed alternative clinical coatings [85]. Co-substitution can also be used to enhance the properties of such polymers with a view to their use in blood-contacting medical devices [189,190], for example water-soluble hemocompatible, sulfo-fluoropolymers [191]. In an alternative approach to antithrombotic effects, degradable amino acid ester-substituted polyphosphazenes have been investigated as NO-releasing coatings via cosubstitution with S-nitrosothiols [192,193].…”