| To address the limitations of systemic drug delivery, localized drug delivery systems (LDDS) based on nano-engineered drug-releasing implants are recognized as a promising alternative and have received considerable attention. Titania nanotube arrays (TNTs) fabricated by a simple, self-ordering electrochemical process have emerged as one of the most reliable contenders for these applications due to their excellent biocompatibility, bioactivity and special hollow nano-structure.Titania nanotube arrays on pure titanium sheets were obtained by a self-ordering electrochemical anodization process in the glycerol/H2O electrolytes containing F- in this paper. Then, anti-inflammatory analgesic drugs loxoprofen sodium (LS) used as model drug were loaded into TNTs by vacuum drying to study the influence of crystalline phase on loading and release of LS. Results indicated that the loading of LS on amorphous TNTs was more than that on anatase ones and different phases of TNTs loaded by model drug had the same drug release characteristics.Firstly, to achieve a significant improvement in the drug release characteristics with reduced burst release and prolonged overall release, CaSiO3 coating was deposited on the surface of titania nanotube arrays by a simple process called "alternative loop immersion method (ALIM)". To study the effect of ALIM, TNTs with different crystal structures were produced by repeated cycles of soaking and zinc doping. The results showed that the amount of CaSiO3 deposited increased with the number of immersion treatments. The ability of CaSiO3 to induce the formation of apatite layer was excellent and more significant in case of ALIM treated amorphous TNTs compared to that of anatase TNTs. Moreover, Zn doped CaSiO3 prepared by adding a certain concentration of zinc nitrate into the soaking system exhibited higher chemical stability and enhanced antibacterial activity.Secondly, electrochemical deposition method was also adopted to prepare CaSiO3 coating on the surface of TNTs, which was conducted in an electrolyte composed of 1 g/1 nano-SiO2 (typical size≈15±5 nm) and 0.042 M Ca(NO3)2 under the following conditions:pH 4.2,0.8 mA/cm2 current density,30 min and 65℃. The results showed that the amount of CaSiO3 deposited increased with the concentration of electrolyte, current density, deposition time and temperature, decreased with the initial pH of electrolyte. A significant improvement in the drug release characteristics with reduced burst release (from 83% to 63%) and sustained release (from 11 days to more than 15 days) was observed by codeposition of drug loading.Thirdly, we present a new implantable drug delivery system that combines mesoporous calcium silicate coating with nanotube structures to achieve a controllable drug release of water soluble and antiphlogistic drug loxoprofen sodium. The morphological, structural and textural properties were well characterized by SEM, XRD, N2 adsorption/desorption and FTIR, respectively. The results showed that TiO2 nanotubes/mesoporous calcium silicate composites (TNT/MCS) were successfully prepared by a simple template method and the deposition of MCS increased with the soaking time and the rate of biological mesoporous calcium silicate deposited on amorphous TiO2 nanotubes was more excellent than anatase TiO2 nanotubes. Meanwhile, Zn-incorporated mesoporous calcium silicate coating produced by adding a certain concentration of zinc nitrate into the soaking system could obtain improved chemical stability. A significant improvement in the drug release characteristics with reduced burst release (from 83% to 68%) and sustained release (from 11 days to more than 15 days) was demonstrated. |
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