The electrochemically engineered nanotubular titania surfaces for controlled and sustained delivery of drugs and drug carriers

Abstract

Limitations of systemic therapy and poorly soluble drugs are persistent problems in pharmaceutical science. A promising alternative to improving drug efficacy and bioavailability is local therapy. Mesoporous structures such as Titania nanotube arrays (TNT) prepared by self-ordering electrochemical process have attracted considerable attention for the development of new implants for local delivery of therapeutics. In this work, we present a drug delivery system based on surface coating on TNT for controlled and extended delivery of poorly water-soluble drugs. TNT layers of highly ordered and vertically aligned nanotubes (20 μm long with diameters of 100 nm) were prepared by the anodization of titanium foil. Indomethacin, an anti-inflammatory drug, was used as an example of a poorly soluble (hydrophobic) drug. Polymeric micelle, D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) loaded with indomethacin was used as the model of drug nanocarrier. Upon drug loading, TNT was coated with thin films of polymers prepared by different techniques: plasma polymerisation (poly-allylamine) and dip-coating (chitosan and poly (lactic-coglycolic) acid, PLGA). TNT implants before and after drug loading and polymer deposition were characterised by scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS). The release of drug and drug carrier was monitored using UV-Vis spectroscopy over 3-4 weeks. The results confirm that a thin polymer film on TNT can considerably extend the release of drugs and drug-loaded polymeric micelles with minor burst release over a period of more than 4 weeks, demonstrating much potential for the use of TNT in bone implant applications.