Loading method for discrete drug depots on implant surfaces

Abstract

Modern biomedical engineering focuses more and more on the development of implant-associated local drug delivery systems for many different applications like stents for the treatment of coronary artery disease. A common method to deposit drugs on implants is their integration within a polymeric coating, which might however be contributor of adverse cardiac events. Moreover, modern implants pursue multimodal and time-controlled approaches, which require more sophisticated drug loading methods. In this context, a loading method based on surface depots that are selectively filled with drugs using a drop-on-demand printhead is investigated. As a first step small drug depots were produced by abrasive or additive laser-based methods on or into the surface of the implant. The range of the depot volumes varies between 1.4×105 and 1×107 μm3. These depots (cavity or tubes) can be filled with pure drugs, drug-polymer-mixtures and/or covered with biodegradable polymers using a piezoelectric drop-on-demand printhead. Therefore, the drugs are dissolved in methanol, ethanol or dimethyl sulfoxide (DMSO). The minimal droplet volume is about 100 pl. The quantity of drug per depot is specified by the number of droplets that are printed into the depots. The proof of principle of the loading method could be demonstrated on stainless steel samples as model implant surface. Drug depots were successfully filled with fluorescein disodium salt, dissolved in a mixture of 50 % DMSO and 50 % ethanol. Further drug depots were loaded with acetylsalicylic acid (ASS), dissolved in pure DMSO. Because of the low volume of a single droplet the depots could be filled very precisely. © 2012 by Walter de Gruyter Berlin Boston.