Evolution of drug-eluting biomedical implants for sustained drug delivery

Abstract

In the field of drug delivery, the most commonly used treatments have traditionally been systemically delivered using oral or intravenous administration. The problems associated with this type of delivery is that the drug concentration is controlled by first pass metabolism, and therefore may not always remain within the therapeutic window. Implantable drug delivery systems (IDDSs) are an excellent alternative to traditional delivery because they offer the ability to precisely control the drug release, deliver drugs locally to the target tissue, and avoid the toxic side effects often experienced with systemic administration. Since the creation of the first FDA-approved IDDS in 1990, there has been a surge in research devoted to fabricating and testing novel IDDS formulations. The versatility of these systems is evident when looking at the various biomedical applications that utilize IDDSs. This review provides an overview of the history of IDDSs, with examples of the different types of IDDS formulations, as well as looking at current and future biomedical applications for such systems. Though there are still obstacles that need to be overcome, ever-emerging new technologies are making the manufacturing of IDDSs a rewarding therapeutic endeavor with potential for further improvements.

Keywords: Biomedical implant applications; Biomedical implants; Controlled drug release; Drug delivery; Drug eluting biomaterials; Drug-eluting biomedical implant; Sustained drug release.

Figure 1.

Representative drawings of various IDDSs. A) Hollow titania nanotube arrays can be filled with a payload to be delivered. B) In situ forming implants such as hydrogels can be activated to begin the polymerization process via external triggers such as light and temperature. C) Polymer-coated drug-eluting stents versus bare metal cardiovascular stents offer the benefit of delivering anti-proliferative drugs to decrease the incidence of in-stent restenosis. D) Implantable reservoir based contraceptive implants are a cost effective and minimally invasive alternative to IUDs.

Figure 2.

Representative image of the novel microchip and pedicle screw IDDS described by Eltorai et. al. [137] using microchip technology patented by Santini Jr. et al. [139]. A) The hollow head of the screw holds the drug-eluting microchip. B) The microchip design is such that the substrate contains the drug to be delivered and drug release is achieved by electrical stimulation to the anode/cathode material.