Advances in nanoscience and engineering have led to development of several novel drug delivery platforms where the size, size distribution, porosity, geometry and surface functionality can be controlled at the nanoscale.  Nanodelivery platforms such as nanoparticles, quantum dots and nanotubes have been reported in literature to have potential applications in drug delivery.  We have developed well controlled titania nanotubular platforms and have demonstrated their efficacy as drug eluting interfaces.  Such nanoscale architectures could be useful for implantable medical devices such as orthopedic implants, vascular stents and dental implants. The number of patients in need of implants in United States has grown rapidly in last decade.  It is expected that by 2010 more than 4.4 million people will have at least one internal fixation device and more than 1.3 million people will have an artificial joint.  Typically after such implant surgery, the patient receives a drug therapy regimen to prevent infection and inflammation; and to induce appropriate integration of the device with the natural tissue.  Drugs such as antibiotics, anti-inflammatory drugs and growth factors are prescribed to be taken either orally, intravenously, intramuscularly or topically.  However, several prescribed drugs are not effective when delivered via these routes.  Antibiotics such as Gentamicin and Neomycin are absorbed from the small intestine and then travel through the portal vein to the liver, where it is inactivated. Therefore, it can only be given intravenously, intramuscularly or topically.  Anti-inflammatory drugs such as Paclitaxel and Actinomycin D; and growth factors such as BMP-2 and FGF are often delivered intravenously or topically.  However, delivery via the systemic routes is often not effective because the drug cannot readily reach the implant-tissue interface, particularly in necrotic or avascular tissue left after surgery.  This limitation cannot be overcome with increased systemic doses because of the organ toxicity associated with drugs at higher concentrations.  Thus, local drug therapy has become an accepted and common adjunct to systemic drug delivery.  This not only offers the advantages of a high localized drug concentration without any systemic toxicity but is also an effective way of delivering drugs right at the site of implantation.  Several techniques have been proposed in literature to delivery drugs locally at the site of implantation.  For example, in case of orthopedic implants, bone cements can be loaded with antibiotics or growth factors can be adsorbed directly on implant surface, in collagen sponges, or in porous coatings; whereas in case of vascular stents, the drugs can be delivery either by diffusion through or degradation of polymer based matrix or reservoir systems.  However, there are several shortcomings of these proposed localized drug delivery techniques including limited chemical stability, local inflammatory reactions due to material composition, and lack of controlled release kinetics from the coatings.

The proposed nanotube based drug localized delivery system offers several advantages over some of the current delivery techniques.  Titania (native oxide TiO2 on the surface of Ti) has been used in implantable devices since the 1970s.  As a biocompatible material, titanium and its alloys, particularly Ti-6Al-4V is extensively used in orthopedic and dental implants.  Further, the biocompatibility of metal-oxides has already been proven as the materials have current clinical applications in orthopedic prostheses and dental implants.  Our technique of producing well controlled nanotubes with anodization provides ease of control over the size and configuration of structure, with maintenance of mechanical properties that is otherwise not possible.  Further, the nanotubes can be fabricated on any three dimensional non-planar surfaces, thus making it readily adaptable to current implant technology.  FThe tube diameter, wall thickness and length can be easily modified to satisfy the individually specific requirements of the drug to be delivered (i.e. the size of the drug molecule and release rates).  It has been shown that the length of the nanotube array can be varied anywhere from 200 nm to 360 µm, the thickness of the nanotube walls from 5nm to 34nm, and the nanotube pore diameter from 12nm to 180nm.  Further, these surfaces exhibit very hydrophilic behavior (contact angels ≈ 0º), which can be easily adjusted by modification with organic molecules.   However, their wettability has been shown to persist during prolonged storage at room temperature.  Thus, the large surface area of the nanotube-array structure and the ability to precisely tune pore size, wall-thickness, and nanotube length to optimize biotemplating properties along with their surface characteristics are among the many desirable properties to use these types of surfaces as drug eluting coatings for implantable devices.