Deciphering platinum dissolution in neural stimulation electrodes: Electrochemistry or biology?

Platinum (Pt) is the metal of choice for electrodes in implantable neural prostheses like the cochlear implants, deep brain stimulating devices, and brain-computer interfacing technologies. However, it is well known since the 1970s that Pt dissolution occurs with electrical stimulation. More recent clinical and in vivo studies have shown signs of corrosion in explanted electrode arrays and the presence of Pt-containing particulates in tissue samples. The process of degradation and release of metallic ions and particles can significantly impact on device performance. Moreover, the effects of Pt dissolution products on tissue health and function are still largely unknown. This is due to the highly complex chemistry underlying the dissolution process and the difficulty in decoupling electrical and chemical effects on biological responses. Understanding the mechanisms and effects of Pt dissolution proves challenging as the dissolution process can be influenced by electrical, chemical, physical, and biological factors, all of them highly variable between experimental settings. By evaluating comprehensive findings on Pt dissolution mechanisms reported in the fuel cell field, this review presents a critical analysis of the possible mechanisms that drive Pt dissolution in neural stimulation in vitro and in vivo. Stimulation parameters, such as aggregate charge, charge density, and electrochemical potential can all impact the levels of dissolved Pt. However, chemical factors such as electrolyte types, dissolved gases, and pH can all influence dissolution, confounding the findings of in vitro studies with multiple variables. Biological factors, such as proteins, have been documented to exhibit a mitigating effect on the dissolution process. Other biological factors like cells and fibro-proliferative responses, such as fibrosis and gliosis, impact on electrode properties and are suspected to impact on Pt dissolution. However, the relationship between electrical properties of stimulating electrodes and Pt dissolution remains contentious. Host responses to Pt degradation products are also controversial due to the unknown chemistry of Pt compounds formed and the lack of understanding of Pt distribution in clinical scenarios. The cytotoxicity of Pt produced via electrical stimulation appears similar to Pt-based compounds, including hexachloroplatinates and chemotherapeutic agents like cisplatin. While the levels of Pt produced under clinical and acute stimulation regimes were typically an order of magnitude lower than toxic concentrations observed in vitro, further research is needed to accurately assess the mass balance and type of Pt produced during long-term stimulation and its impact on tissue response. Finally, approaches to mitigating the dissolution process are reviewed. A wide variety of approaches, including stimulation strategies, coating electrode materials, and surface modification techniques to avoid excess charge during stimulation and minimise tissue response, may ultimately support long-term and safe operation of neural stimulating devices.

Non-degradable polymer nanocomposites for drug delivery.

INTRODUCTION: The need to optimize therapeutic outcomes while minimizing side effects is a major driving force for research and development in the controlled drug delivery field. Polymer nanocomposites (NCs) are an emerging class of materials with remarkable potential for controlled drug delivery. There are a range of release mechanisms that characterize polymer NC systems, and these may be perturbed not only by the addition of nanofillers, but also by the type of drug and the interactions of the drug with the components of the system. AREAS COVERED: The focus of this review is on non-degradable polymer NC systems. In particular, the types of drug delivery approach from these polymer NCs and the theoretical models developed to describe those approaches are discussed. The importance of component interactions and factors affecting drug delivery from polymer NCs is also addressed. EXPERT OPINION: Despite the remarkable potential and extensive research being conducted on polymer NCs for use in drug delivery, commercialization and large-scale production are limited by the cost and difficulty in consistently producing fully exfoliated NCs. A continuing challenge for the field is to understand better the key interactions and structure-property relationships arising from different polymer, filler and drug combinations.

Biostability and biological performance of a PDMS-based polyurethane for controlled drug release.

Polymers have been used to deliver therapeutic agents in a range of medical devices with drug eluting stents being the most widespread current application. Although polymers enable controlled release of a therapeutic agent, the polymeric surface has been reported to provide suboptimal biocompatibility and haemocompatibility and it has been suggested that currently used polymers may be at least partly responsible for the late adverse events observed in intravascular stent systems. In this study, the biostability and biological performance of a siloxane-based polyurethane elastomer (E2A) demonstrating excellent long-term biostability in the unloaded state was investigated following incorporation of a therapeutic agent. After implantation in an ovine model for 6 months, samples were assessed using SEM and ATR-FTIR to determine changes in the surface chemical structure and morphology of the materials and tensile testing was used to examine changes in bulk characteristics. Biological response was assessed using in vitro cytotoxicity testing and histological analysis. Results indicated that incorporation of 25mg/g dexamethasone acetate (DexA) into the siloxane-based polyurethane resulted in no significant difference in the biostability and biocompatibility of the material. Some level of cytotoxic potential was exhibited which was believed to result from residual DexA leaching from samples during the extraction process. These findings suggest that E2A is a potential candidate for a delivery vehicle of therapeutic agents in implantable drug delivery applications.