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 1.4x10 5 and 1x10 7 ȝm³. 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.

Influence of the Volatility of Solvent on the Reproducibility of Droplet Formation in Pharmaceutical Inkjet Printing

“…However, when using solvent mixtures, the solubility of the desired API in the solvent mixture must be considered. In addition, the use of highly volatile solvents in inkjet printing can be beneficial to minimize fabrication time [ 35 ].…”

“…High volatilities may be beneficial for fast inkjet printing, as the solvent of the printed droplets of the drug solution quickly evaporates from the substrate, leaving behind the drug to be delivered. Especially, applications such as the filling of reservoirs can benefit from high evaporation rates [ 35 ].…”

“…However, there is the risk of nozzle clogging because of drug deposits from evaporating drug solution on the nozzle of the printhead, especially when using highly volatile solvents [ 7 , 35 , 36 ]. In this context, the drug concentration in the drug solution also plays a crucial role.…”

Machining of Biocompatible Ceramics with Femtosecond Laser Pulses

“…Thinking of drug-eluting applications these depots would be capable to comprise a much larger quantity of medical drugs as compared to the exemplary drug depots discussed in Ref. [3]. The unmachined surface surrounding the holes does not reveal any evidence of material degradation such as micro-cracks as discussed above which is demonstrated in Figure 3.…”