Conventional drug delivery systems have limitations according to their toxicity and poor solubility, bioavailability, stability, and pharmacokinetics (PK). Here, we highlight the importance of functionalized titanate nanotubes (TNTs) as targeted drug delivery systems. We discuss the differences in the physicochemical properties of TNTs and carbon nanotubes (CNTs) and focus on the use of functionalization to improve their characteristics. TNTs are promising materials for drug delivery systems because of their superb properties compared with CNTs, such as their processability, wettability, and biocompatibility. Functionalization improves nanoparticles (NPs) via their surface modification and enables them to achieve the targeted therapy.

Titanate nanotubes (TNTs) are promising vectors for drug delivery due to their unique physicochemical properties such as biocompatibility, mechanical strength, and chemical resistivity. However, considering their strong hydrophilicity, pristine TNTs exert very limited permeability through the intestinal cell layer. The aim of this study was to turn the surface characteristics and thus enhance the permeability of TNTs by functionalization. TNTs were functionalized with trichloro(octyl)silane (TCOS) and magnesium stearate (MgSt). Carbon content and surface free energy of the functionalized TNTs were detected to evaluate the effectiveness of functionalization, by using CHNS analytical and optical contact angle (OCA) measurements, respectively. Caco-2 cell line was applied to test the permeability and the cytotoxicity of the samples. Cytotoxicity was evaluated by using MTT assay. The results revealed that the surface characteristics of TNTs may be adjusted in a wider range with TCOS-TNT than with St, but the samples show higher toxicity. Silane functionalized TNTs may be safe up to 1 mg/ml, while St functionalized TNTs up to 2 mg/ml concentration. The preparation method of MgSt-TNT was also superior from the aspect of environmental safety. The permeability was suitable for samples with moderate hydrophobicity (aqueous contact angle 60-90°).

Recently, there has been an increasing interest in the application of nanotubular structures for drug delivery. There are several promising results with carbon nanotubes; however, in light of some toxicity issues, the search for alternative materials has come into focus. The objective of the present study was to investigate the influence of the applied solvent on the composite formation of titanate nanotubes (TNTs) with various drugs in order to improve their pharmacokinetics, such as solubility, stability, and bioavailability. Composites were formed by the dissolution of atenolol (ATN) and hydrochlorothiazide (HCT) in ethanol, methanol, 0.01 M hydrochloric acid or in ethanol, 1M sodium hydroxide, dimethylformamide (DMF), dimethyl sulfoxide (DMSO), respectively, and then they were mixed with a suspension of TNTs under sonication for 30 min and vacuum-dried for 24 h. The structural properties of composites were characterized by SEM, TEM, FT-IR, differential scanning calorimetry (DSC), thermogravimetric (TG) analysis, and optical contact angle (OCA) measurements. Drug release was determined from the fast disintegrating tablets using a dissolution tester coupled with a UV–Vis spectrometer. The results revealed that not only the good solubility of the drug in the applied solvent, but also the high volatility of the solvent, is necessary for an optimal composite-formation process.

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