Abstract:A pH-sensitive stimulus-response system for controlled drug release was prepared by modifying nano porous silica nanoparticles (NPSNPs) with poly(4-vinylpyridine) using a bismaleimide as linker. At physiological pH values, the polymer serves as gate keeper blocking the pore openings to prevent the release of cargo molecules. At acidic pH values as they can occur during a bacterial infection, the polymer strains become protonated and straighten up due to electrostatic repulsion. The pores are opened and the cargo is released. The drug chlorhexidine was loaded into the pores because of its excellent antibacterial properties and low tendency to form resistances. The release was performed in PBS and diluted hydrochloric acid, respectively. The results showed a considerably higher release in acidic media compared to neutral solvents. Reversibility of this pHdependent release was established. In vitro tests proved good cytocompatibility of the prepared nanoparticles. Antibacterial activity tests with Streptococcus mutans and Staphylococcus aureus revealed promising perspectives of the release system for biofilm prevention. The developed polymer-modified silica nanoparticles can serve as an efficient controlled drug release system for long-term delivery in biomedical applications, such as in treatment of biofilm-associated infections, and could, for example, be used as medical implant coating or as components in dental composite materials.

For several centuries silver is known for its antibacterial effects. The middle ear is an interesting new scope for silver application since chronic inflammations combined with bacterial infection cause complete destruction of the fragile ossicle chain and tympanic membrane. The resulting conductive deafness requires tympanoplasty for reconstruction. Strategies to prevent bacterial growth on middle ear prostheses are highly recommended. In this study, rabbits were implanted with Bioverit® II middle ear prostheses functionalized with silver containing dense and nanoporous silica films which were compared with pure silica coatings as well as silver sulfadiazine cream applied on nanoporous silica coating. The health status of animals was continuously monitored; blood was examined before and after implantation. After 21 days, the middle ears were inspected; implants and mucosal samples were processed for electron microscopy. Autopsies were performed and systemic spreading of silver was chemically analyzed exemplarily in liver and kidneys. For verification of direct cytotoxicity, NIH 3T3 cells were cultured on similar silver containing silica coatings on glass up to 3 days. In vitro a reduced viability of fibroblasts adhering directly on the samples was detected compared to cells growing on the surrounding plastic of the same culture dish. In transmission electron microscopy, phagocytosed silver silica fragments, silver sulfadiazine cream as well as silver nanoparticles were noticed inside endosomes. In vivo, clinical and post mortem examinations were inconspicuous. Chemical analyses showed no increased silver content compared to controls. Mucosal coverages on almost all prostheses were found. But reduction of granulation tissue was only obvious around silver-coated implants. Single necroses and apoptosis in the mucosa were correlated by intracellular accumulation of metallic silver. For confirming supportive healing effects of middle ear implants, silver ion aggregates need to be tested in the future to optimize biocompatibility while assuring bactericidal effects in the middle ear.