Functional ferrocene polymer multilayer coatings for implantable medical devices: Biocompatible, antifouling, and ROS-sensitive controlled release of therapeutic drugs.

Bacterial infections and the formation of biofilms on the surface of implantable medical devices are critical issues that cause device failure. Implantable medical devices, such as drug delivery technologies, offer promising benefits for targeted and prolonged drug release, but a number of common disadvantages arise that include inadequate release and side effects. Organic film coatings for antifouling and drug delivery are expected to overcome these challenges. Ferrocene polymer-based multifunctional multilayer films were prepared to control the reactive oxygen species (ROS)-responsive release of therapeutic agents while maintaining an antifouling effect and improving biocompatibility. Polymers based on ferrocene and polyethylene glycol were prepared by controlling the molar ratio of carboxylate and amine groups. Layer-by-layer deposition was optimized to achieve the linear growth and self-assembly of dense and stable films. Outstanding anti-biofilm activity (~91% decrease) could be achieved and the films were found to be blood compatible. Importantly, the films effectively incorporated hydrophobic drugs and exhibited dual-responsive drug release at low pH and under ROS conditions at physiological pH. Drug delivery to MCF-7 breast cancer cells was achieved using a Paclitaxel loaded film, which exhibited an anticancer efficacy of 62%. STATEMENT OF SIGNIFICANCE: Healthcare associated infection is caused by the formation of a biofilm by bacteria on the surface of a medical device. In order to solve this, extensive research has been conducted on many coating technologies. Also, a method of chemical treatment by releasing the drug when it enters the body by loading the drug into the coating film is being studied. However, there is still a lack of technology that can achieve both functions of preventing biofilm production and drug delivery. Therefore, in this study, a multilayer thin film that supports drug and inhibits biofilm formation was prepared through Layer-by-Layer coating of a polymer containing PEG to prevent adsorption. As such, it helps the design of multifunctional coatings for implantable medical devices.

Novel carboxylated ferrocene polymer nanocapsule with high reactive oxygen species sensitivity and on-demand drug release for effective cancer therapy.

Multidrug resistance (MDR) is a major clinical issue leading to substantial reductions in the intracellular levels of anticancer drugs. To overcome MDR, stimulus-responsive polymeric nanotherapeutics that facilitate drug release and cellular uptake at target sites have emerged as promising tools for safe and effective cancer treatment. Among these nanotherapeutics, reactive oxygen species (ROS)-responsive nanocapsules are ideal carriers, as abnormally increased ROS levels can drive controlled drug release at target sites. In this study, we developed novel, high ROS-responsive carboxylated ferrocene nanocapsules (CFNCs) using solvents of different polarities for effective multidrug-resistant cancer therapy. The CFNCs were prepared via the self-assembly of an amphiphilic carboxylated ferrocene polymer composed of a hydrophilic COOH segment and a hydrophobic ferrocenylmethyl methacrylate segment possessing a ROS-responsive group. The size and ROS sensitivity of self-assembled CFNCs could be controlled by using solvents of different polarities during the simple nanoprecipitation process. The CFNCs showed a high loading content (approximately 30 wt%) and on-demand release of paclitaxel under both normal and tumor-mimicking conditions, and exhibited synergistic anticancer effects in multidrug-resistant colorectal cancer cells (HCT-15). Our findings suggest that CFNCs can be applied as carriers for effective cancer therapy.

Reactive oxygen species (ROS)-responsive ferrocene-polymer-based nanoparticles for controlled release of drugs.

Ferrocene-containing nanoparticles show reversible redox activity that could trigger drug release mediated by reactive oxygen species (ROS). In this study, four ferrocene-containing polymers, comprising ferrocenylmethyl methacrylate (FMMA)-methacrylic acid (MA) random copolymers, i.e., poly(FMMA-r-MA), were synthesized via radical polymerization, resulting in self-assembled ferrocene nanoparticles (FNPs) with outstanding performance in environments in which ROS are present. These spherical FNPs have tunable diameters ranging from 270 nm to 180 nm and surface charges from -20 mV to -50 mV. Importantly, the diameters and surface charges of the FNPs changed dramatically after 2 h of post-treatment using 0.4 M hydrogen peroxide (H2O2) as the oxidant, indicating that the FNPs were highly ROS-sensitive. Furthermore, the controlled release of a model drug from the FNPs, reflected in the release profiles, indicates that these novel FNPs could be potentially used as drug carriers for the effective therapy of ROS-related diseases such as cancer and inflammation.