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TiO 2 nanotube platforms for smart drug delivery: a review

View Article: PubMed Central - PubMed

ABSTRACT

Titania nanotube (TNT) arrays are recognized as promising materials for localized drug delivery implants because of their excellent properties and facile preparation process. This review highlights the concept of localized drug delivery systems based on TNTs, considering their outstanding biocompatibility in a series of ex vivo and in vivo studies. Considering the safety of TNT implants in the host body, studies of the biocompatibility present significant importance for the clinical application of TNT implants. Toward smart TNT platforms for sustainable drug delivery, several advanced approaches were presented in this review, including controlled release triggered by temperature, light, radiofrequency magnetism, and ultrasonic stimulation. Moreover, TNT implants used in medical therapy have been demonstrated by various examples including dentistry, orthopedic implants, cardiovascular stents, and so on. Finally, a future perspective of TNTs for clinical applications is provided.

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Schematic illustration of four methods for drug loading and profiles of drug release from TNTs.Notes: (A) Four approaches for drug loading using HRP as a model drug; (B) relative intensity of reflected light (wavelength 550 nm) as a function of time after exposure of HRP-loaded amphiphilic TNTs to PBS without illumination (curve a), 50% UV illumination (curve b), full UV illumination (curve c) and the release of HRP in TNTs without any surface modification (curve d); (C) optical images of the solution containing indicator substrate (ABTS) and H2O2 before HRP release (left) and after HRP release without (middle) and with UV illumination for 40 minutes (right); (D) relative reflected intensity changes for the four different types of nanotubes used in this study (according to the scheme of A) with and without UV illumination; (E) schematic illustration of the HRP release under UV illumination. Reprinted with permission from Song YY, Schmidt-Stein F, Bauer S, Schmuki P. Amphiphilic TiO2 nanotube arrays: an actively controllable drug delivery system. J Am Chem Soc. 2009;131:4230–4232.16 Copyright (2009) American Chemical Society.Abbreviations: APTES, 3-aminopropyltriethoxysilane; HRP, horseradish peroxidase; OPDA, octadecylphosphonic acid; PBS, phosphate-buffered saline; TNT, titania nanotube; UV, ultraviolet.
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f6-ijn-11-4819: Schematic illustration of four methods for drug loading and profiles of drug release from TNTs.Notes: (A) Four approaches for drug loading using HRP as a model drug; (B) relative intensity of reflected light (wavelength 550 nm) as a function of time after exposure of HRP-loaded amphiphilic TNTs to PBS without illumination (curve a), 50% UV illumination (curve b), full UV illumination (curve c) and the release of HRP in TNTs without any surface modification (curve d); (C) optical images of the solution containing indicator substrate (ABTS) and H2O2 before HRP release (left) and after HRP release without (middle) and with UV illumination for 40 minutes (right); (D) relative reflected intensity changes for the four different types of nanotubes used in this study (according to the scheme of A) with and without UV illumination; (E) schematic illustration of the HRP release under UV illumination. Reprinted with permission from Song YY, Schmidt-Stein F, Bauer S, Schmuki P. Amphiphilic TiO2 nanotube arrays: an actively controllable drug delivery system. J Am Chem Soc. 2009;131:4230–4232.16 Copyright (2009) American Chemical Society.Abbreviations: APTES, 3-aminopropyltriethoxysilane; HRP, horseradish peroxidase; OPDA, octadecylphosphonic acid; PBS, phosphate-buffered saline; TNT, titania nanotube; UV, ultraviolet.

Mentions: For in-depth study of the controlled release of drugs or therapeutics using TNTs, light-sensitive release is also a promising strategy. Song et al reported that amphiphilic TNTs were used to provide a highly controllable drug release system based on a hydrophobic cap (monolayer of OPDA) on the top of TNTs, which can be removed by ultraviolet (UV)-induced chain scission. In this work, different drug-loading approaches were used to study hydrophilic drug release from the amphiphilic TNTs as outlined in Figure 6A.16 For reference, unmodified TNTs were used to load horseradish peroxidase (HRP) by simple immersion (Figure 6A, case I), which leads to physisorbed HRP molecules within TNTs. In the second case, TNTs capped with OPDA were immersed in HRP (Figure 6A, case II), which also leads to physisorbed drug molecules in the lower part of TNTs but remains trapped by OPDA after evaporation of the surfactant, dimethyl sulfoxide. TNTs capped without OPDA were used for HRP grafting by a 3-aminopropyltriethoxysilane/vitamin C monolayer linker covalently attached (Figure 6A, case III). TNTs capped with OPDA were attached to the HRP in the lower part of TNT wall as in case III (Figure 6A, case IV). For different loading approaches, the HRP release characteristics are presented in Figure 6B–E. From these results, it was demonstrated that UV light could make chain scission and then induce drug release from TNTs, thus opening potential perspectives for the drug delivery systems based on light control.


TiO 2 nanotube platforms for smart drug delivery: a review
Schematic illustration of four methods for drug loading and profiles of drug release from TNTs.Notes: (A) Four approaches for drug loading using HRP as a model drug; (B) relative intensity of reflected light (wavelength 550 nm) as a function of time after exposure of HRP-loaded amphiphilic TNTs to PBS without illumination (curve a), 50% UV illumination (curve b), full UV illumination (curve c) and the release of HRP in TNTs without any surface modification (curve d); (C) optical images of the solution containing indicator substrate (ABTS) and H2O2 before HRP release (left) and after HRP release without (middle) and with UV illumination for 40 minutes (right); (D) relative reflected intensity changes for the four different types of nanotubes used in this study (according to the scheme of A) with and without UV illumination; (E) schematic illustration of the HRP release under UV illumination. Reprinted with permission from Song YY, Schmidt-Stein F, Bauer S, Schmuki P. Amphiphilic TiO2 nanotube arrays: an actively controllable drug delivery system. J Am Chem Soc. 2009;131:4230–4232.16 Copyright (2009) American Chemical Society.Abbreviations: APTES, 3-aminopropyltriethoxysilane; HRP, horseradish peroxidase; OPDA, octadecylphosphonic acid; PBS, phosphate-buffered saline; TNT, titania nanotube; UV, ultraviolet.
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Related In: Results  -  Collection

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f6-ijn-11-4819: Schematic illustration of four methods for drug loading and profiles of drug release from TNTs.Notes: (A) Four approaches for drug loading using HRP as a model drug; (B) relative intensity of reflected light (wavelength 550 nm) as a function of time after exposure of HRP-loaded amphiphilic TNTs to PBS without illumination (curve a), 50% UV illumination (curve b), full UV illumination (curve c) and the release of HRP in TNTs without any surface modification (curve d); (C) optical images of the solution containing indicator substrate (ABTS) and H2O2 before HRP release (left) and after HRP release without (middle) and with UV illumination for 40 minutes (right); (D) relative reflected intensity changes for the four different types of nanotubes used in this study (according to the scheme of A) with and without UV illumination; (E) schematic illustration of the HRP release under UV illumination. Reprinted with permission from Song YY, Schmidt-Stein F, Bauer S, Schmuki P. Amphiphilic TiO2 nanotube arrays: an actively controllable drug delivery system. J Am Chem Soc. 2009;131:4230–4232.16 Copyright (2009) American Chemical Society.Abbreviations: APTES, 3-aminopropyltriethoxysilane; HRP, horseradish peroxidase; OPDA, octadecylphosphonic acid; PBS, phosphate-buffered saline; TNT, titania nanotube; UV, ultraviolet.
Mentions: For in-depth study of the controlled release of drugs or therapeutics using TNTs, light-sensitive release is also a promising strategy. Song et al reported that amphiphilic TNTs were used to provide a highly controllable drug release system based on a hydrophobic cap (monolayer of OPDA) on the top of TNTs, which can be removed by ultraviolet (UV)-induced chain scission. In this work, different drug-loading approaches were used to study hydrophilic drug release from the amphiphilic TNTs as outlined in Figure 6A.16 For reference, unmodified TNTs were used to load horseradish peroxidase (HRP) by simple immersion (Figure 6A, case I), which leads to physisorbed HRP molecules within TNTs. In the second case, TNTs capped with OPDA were immersed in HRP (Figure 6A, case II), which also leads to physisorbed drug molecules in the lower part of TNTs but remains trapped by OPDA after evaporation of the surfactant, dimethyl sulfoxide. TNTs capped without OPDA were used for HRP grafting by a 3-aminopropyltriethoxysilane/vitamin C monolayer linker covalently attached (Figure 6A, case III). TNTs capped with OPDA were attached to the HRP in the lower part of TNT wall as in case III (Figure 6A, case IV). For different loading approaches, the HRP release characteristics are presented in Figure 6B–E. From these results, it was demonstrated that UV light could make chain scission and then induce drug release from TNTs, thus opening potential perspectives for the drug delivery systems based on light control.

View Article: PubMed Central - PubMed

ABSTRACT

Titania nanotube (TNT) arrays are recognized as promising materials for localized drug delivery implants because of their excellent properties and facile preparation process. This review highlights the concept of localized drug delivery systems based on TNTs, considering their outstanding biocompatibility in a series of ex vivo and in vivo studies. Considering the safety of TNT implants in the host body, studies of the biocompatibility present significant importance for the clinical application of TNT implants. Toward smart TNT platforms for sustainable drug delivery, several advanced approaches were presented in this review, including controlled release triggered by temperature, light, radiofrequency magnetism, and ultrasonic stimulation. Moreover, TNT implants used in medical therapy have been demonstrated by various examples including dentistry, orthopedic implants, cardiovascular stents, and so on. Finally, a future perspective of TNTs for clinical applications is provided.

No MeSH data available.


Related in: MedlinePlus