Drug Delivery and Bio Applications

Recent active areas of research which involve the use of nanostructured inorganic materials in biological applications include: controlled drug delivery, the labelling of biological objects, and the building of artificial tissues from nanostructured material composites.144,145

Due to their high surface area and affinity towards positively charged ions in aqueous solution, elongated nanostructured titanates have recently been studied as a possible element in amperometric bio-sensors. It has been shown that the redox mediator Meldola blue146 and such oxygen-transport metalloproteins as haemoglobin147 or myoglobin148 can be easily immobilized on the surface of TiNT, providing efficient electron transfer between biological molecules and the artificial electrode. Such transfer is usually a challenging task due to the bad compatibility between the inorganic materials and the bio-molecules. The improved charge transfer in such systems can be utilized in bio-sensors, e.g. for glucose and NADH.

The studies of ibuprofen adsorption in the pores of TiNT have revealed that the melting temperature of ibuprofen is decreased from 78 °C in the bulk to 66 °C, which is closer to physiological temperatures and might be utilised for controlled drug delivery, following improvements in the technology.149 The use of titanate nanotubes as capsules for drug delivery and controlled release could be developed based upon a combination of several nanotube properties. A high surface area and large pore volume (due in large extent to the internal cavities of the nanotubes), provide nanotubes with the high load capacity required for drug storage. The nanotubular morphology can be potentially beneficial in drug delivery to the targeted tissue. The brittle nature of the nanotube wall can be utilized for the controlled release of the loaded species stimulated by, for example, ultrasound treatment. Finally, another important property of titanate nanotubes which favours them over, for example, silicon dioxide nanotubes, is their slow dissolution in an acid environment rendering them biodegradable.

Titanium surfaces coated with titanate nanofibres produced by the alkaline hydrothermal method can be used as bio-scaffolds for cell cultures, providing enough rigidity and a large macroporous structure suitable for cell growth and nutrition.150 The biocompatibility of fibrous sodium titanate deposited inside the pores of anodized TiO2 nanotube arrays, has been recently demonstrated by observation of the increased growth of hydroxyapatite (HAp) from simulated body fluid.151 The ability to stimulate crystallisation of HAp on the surface of titanates can be related to their good ion-exchange properties. Hence elongated titanate-coated surfaces are potentially useful in the preparation of well-adhered bioactive surface layers on Ti substrates for orthopaedic and dental implants.

Due to the biocompatibility, the specific range of the pore sizes and the unusual topography of anodized TiO2 nanotubes, their interactions with biological cells can be important for understanding the in vivo processes of titanium-based implants. Recently, the effect of the morphology of TiO2 nanotube arrays (including diameter and length) on the adhesion, spreading, growth and differentiation of mesenchymal stem cells was thoroughly studied.152 It was shown that the size of nanotube diameter which most stimulated cell growth and differentiation was approximately 15 nm, while diameters of approximately 100 nm led to drastically increased cell apoptosis.

Further developments in elongated titanates and TiO2 as materials for biotechnology would require comprehensive studies of their cytotoxicity. Improved methods for the filling of nanotube pores with bioactive drug molecules could provide a significant step towards the development of controlled drug delivery systems.

For many applications, it important to produce nanostructured titanates and titanium dioxides in a form that is suitable for industrial processing. It is also attractive to process materials in a flexible textile form for sensors and transducers. Recent studies have demonstrated the possibility of producing composite, electrically conductive fibres containing titanate nanotubes, carbon nanotubes and chitosan.153 The material dispersed typically comprised 1wt% chitosan and 0.3 wt% (SWCN + H-TiNT) mixture in a sonicated aqueous solution. The mixture was coagulated in a bath containing NaOH (10 wt%) in methanol. The presence of SWCNs improved the mechanical, as well as the electrical, properties of the fibres. The resultant fibres showed good bio-compatibility, as evidenced by the adhesion and proliferation of L929 mouse fibroblast cells, and it is suggested that the materials might be suitable for inclusion in biomedical devices such as orthopaedic implants.

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