RESUMO
Glucocorticoids are used intra-operatively in cochlear implant surgeries to reduce the inflammatory reaction caused by insertion trauma and the foreign body response against the electrode carrier after cochlear implantation. To prevent higher systemic concentrations of glucocorticoids that might cause undesirable systemic side effects, the drug should be applied locally. Since rapid clearance of glucocorticoids occurs in the inner ear fluid spaces, sustained application is supposedly more effective in suppressing foreign body and tissue reactions and in preserving neuronal structures. Embedding of the glucocorticoid dexamethasone into the cochlear implant electrode carrier and its continuous release may solve this problem. The aim of the present study was to examine how dexamethasone concentrations in the electrode carrier influence drug levels in the perilymph at different time points. Silicone rods were implanted through a cochleostomy into the basal turn of the scala tympani of guinea pigs. The silicone rods were loaded homogeneously with 0.1, 1, and 10% concentrations of dexamethasone. After implantation, dexamethasone concentrations in perilymph and cochlear tissue were measured at several time points over a period of up to 7 weeks. The kinetic was concentration-dependent and showed an initial burst release in the 10%- and the 1%-dexamethasone-loaded electrode carrier dummies. The 10%-loaded electrode carrier resulted in a more elevated and longer lasting burst release than the 1%-loaded carrier. Following this initial burst release phase, sustained dexamethasone levels of about 60 and 100 ng/ml were observed in the perilymph for the 1 and 10% loaded rods, respectively, during the remainder of the observation time. The 0.1% loaded carrier dummy achieved very low perilymph drug levels of about 0.5 ng/ml. The cochlear tissue drug concentration shows a similar dynamic to the perilymph drug concentration, but only reaches about 0.005-0.05% of the perilymph drug concentration. Dexamethasone can be released from silicone electrode carrier dummies in a controlled and sustained way over a period of several weeks, leading to constant drug concentrations in the scala tympani perilymph. No accumulation of dexamethasone was observed in the cochlear tissue. In consideration of experimental studies using similar drug depots and investigating physiological effects, an effective dose range between 50 and 100 ng/ml after burst release is suggested for the CI insertion trauma model.
RESUMO
The settlement and colonization of marine organisms on submerged man-made surfaces is a major economic problem for many marine industries. The most apparent detrimental effects of biofouling are increased fuel consumption of ships, clogging of membranes and heat exchangers, disabled underwater sensors, and growth of biofoulers in aquaculture systems. The presently common-but environmentally very problematic-way to deal with marine biofouling is to incorporate biocides, which use biocidal products in the surface coatings to kill the colonizing organisms, into the surface coatings. Since the implementation of the International Maritime Organization Treaty on biocides in 2008, the use of tributyltin (TBT) is restricted and thus environmentally benign but effective surface coatings are required. In this short review, we summarize the different strategies which are pursued in academia and industry to better understand the mechanisms of biofouling and to develop strategies which can be used for industrial products. Our focus will be on chemically "inert" model surface coatings, in particular oligo- and poly(ethylene glycol) (OEG and PEG) functionalized surface films. The reasons for choosing this class of chemistry as an example are three-fold: Firstly, experiments on spore settlement on OEG and PEG coatings help to understand the mechanism of non-fouling of highly hydrated interfaces; secondly, these studies defy the common assumption that surface hydrophilicity-as measured by water contact angles-is an unambiguous and predictive tool to determine the fouling behavior on the surface; and thirdly, choosing this system is a good example for "interfacial systems chemistry": it connects the behavior of unicellular marine organisms with the antifouling properties of a hydrated surface coating with structural and electronic properties as derived from ab initio quantum mechanical calculations using the electronic wave functions of oxygen, hydrogen, and carbon. This short review is written to outline for non-experts the hierarchical structure in length- and timescale of marine biofouling and the role of surface chemistry in fouling prevention. Experts in the field are referred to more specialized recent reviews.
