(532e) Development and Evaluation of Minocycline/Rifampicin-Impregnated Silicone Catheters: a Potential Tool for the Treatment of Csf Shunt Infection

Treatment of CSF shunts with antimicrobial agents has shown great potential for preventing shunt infections. Providing a longer period of sustained antibiotic release is an important challenge to the development of clinical shunts for long-term implantation. This study aimed to evaluate the long-term in vitro drug release performance of a cast-molded catheter with a self-assembled silane monolayer coating to provide a tunable release rate. A cast molding approach was used to load minocycline and rifampicin into the silicone precursor prior to curing. Self-assembled perfluorodecyltrichlorosilane (FAS) and octadecyltrichlorosilane (OTS) monolayer and FAS multilayer were deposited on the drug-loaded silicone surface by chemical vapor deposition and molecular vapor deposition, respectively. The morphology of adhered bacteria was observed by scanning electron microscopy and atomic force microscopy. The efficacy of the minocycline and rifampicin was determined by measurement of S. epidermidis adhesion on treated and untreated silicone surface using a colony counting method.

The cast molding approach avoided the microstructural changes observed in samples prepared by the conventional diffusion-controlled antibiotic loading technique and minimized the initial “burst effect” of drug release. In in-vitro studies, different morphologies and structures of S epidermidis colonization were observed on untreated silicone surfaces (compacted multilayered structures) and rifampicin-loaded silicone surfaces (sparsely dispersed, single-layered structures), respectively. Some of the Staphylococcus epidermidis cells which were exposed to the continuously released rifampicin were deformed and the secretion of slime was reduced. Sustained in vitro release from rifampicin-loaded silicone for upwards of 110 days at a level of approximately 2-4 µg/cm2-day was achieved. The rifampicin-loaded silicone decreased bacterial adherence by 99.8% on fresh 8.3% rifampicin-loaded silicone and by 94.8% on rifampicin-loaded silicone surfaces that had been eluted for 90 days. Additionally, FAS layers moderated the burst effect and prolonged the subsequent continuous release to achieve a longer-term delivery. Significant decreases in initial burst effect and enhanced long-term release were observed.

Cast molding can be adapted to a host of pharmacologically active ingredients or combinations as desired. Thus, this technique can be applied to a variety of shunt-based drug release treatments. Moreover, in this study we demonstrate that the FAS coatings are effective in controlling and tuning the drug release rate. This novel coating approach can also create different designs for surface coatings, such as close-to-complete coverage, partial coverage, and patterned coverage that will allow delivery rates to be customized and perhaps even tailored to specific patients.