Nanoengineered drug-releasing Ti wires as an alternative for local delivery of chemotherapeutics in the brain

Karan Gulati1,2, Moom Sinn Aw1, Dusan Losic1,21Ian Wark Research Institute, The University of South Australia, Adelaide, SA, Australia; 2School of Chemical Engineering, The University of Adelaide, Adelaide, SA, AustraliaAbstract: The blood&ndash;brain barrier (BBB) blocks the passage of acti...

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Autores principales:	Gulati K, Sinn Aw M, Losic D
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e60df70c0528473a8203a0be612b4a94
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id	oai:doaj.org-article:e60df70c0528473a8203a0be612b4a94
record_format	dspace
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Gulati K Sinn Aw M Losic D Nanoengineered drug-releasing Ti wires as an alternative for local delivery of chemotherapeutics in the brain
description	Karan Gulati1,2, Moom Sinn Aw1, Dusan Losic1,21Ian Wark Research Institute, The University of South Australia, Adelaide, SA, Australia; 2School of Chemical Engineering, The University of Adelaide, Adelaide, SA, AustraliaAbstract: The blood&ndash;brain barrier (BBB) blocks the passage of active molecules from the blood which makes drug delivery to the brain a challenging problem. Oral drug delivery using chemically modified drugs to enhance their transport properties or remove the blocking of drug transport across the BBB is explored as a common approach to address these problems, but with limited success. Local delivery of drugs directly to the brain interstitium using implants such as polymeric wafers, gels, and catheters has been recognized as a promising alternative particularly for the treatment of brain cancer (glioma) and neurodegenerative disorders. The aim of this study was to introduce a new solution by engineering a drug-releasing implant for local drug delivery in the brain, based on titanium (Ti) wires with titania nanotube (TNT) arrays on their surfaces. Drug loading and drug release characteristics of this system were explored using two drugs commonly used in oral brain therapy: dopamine (DOPA), a neurotransmitter agent; and doxorubicin (DOXO), an anticancer drug. Results showed that TNT/Ti wires could provide a considerable amount of drugs (&gt;170 &micro;g to 1000 &micro;g) with desirable release kinetics and controllable release time (1 to several weeks) and proved their feasibility for use as drug-releasing implants for local drug delivery in the brain.Purpose: In this report, a new drug-releasing platform in the form of nanoengineered Ti wires with TNT arrays is proposed as an alternative for local delivery of chemotherapeutics in the brain to bypass the BBB. To prove this concept, drug loading and release characteristics of two drugs important for brain therapy (the neurotransmitter DOPA and the anticancer drug DOXO) were explored.Methods: Titania nanotube arrays on the surface of Ti wires (TNT/Ti) were fabricated using a simple anodization process, followed by separate loading of two drugs (DOPA and DOXO) inside the nanotube structures. The loading and in vitro release characteristics of prepared TNT/Ti implants were examined using thermogravimetric analysis (TGA) UV-Vis spectroscopy.Results: Scanning electron microscopy studies confirmed that well-ordered, vertically aligned, densely packed nanotube arrays with an average diameter of 170 nm and length 70 &micro;m were formed on the surface of TNT/Ti wires. TGA results showed a total drug loading of 170 &micro;g and 1200 &micro;g inside the TNTs for DOPA and DOXO respectively. Two-phase drug release behavior was observed including a fast release (burst) for the first 6 hours and a prolonged slow release phase for 8 days, both with acceptable dosage and desirable release kinetics. The physical, structural, loading and release characteristics of prepared TNT/Ti implants showed several advantages in comparison with existing and clinically proved brain implants.Conclusion: Our results confirmed that TNT/Ti wires can be successfully employed as a suitable platform to release neurotransmitters such as DOPA and anticancer drugs such as DOXO. Hence, they are a feasible alternative as drug-releasing implants for local drug delivery in the brain to combat neurodegenerative disorders or brain tumors.Keywords: titania nanotubes, brain implants, local drug delivery, dopamine, doxorubicin
format	article
author	Gulati K Sinn Aw M Losic D
author_facet	Gulati K Sinn Aw M Losic D
author_sort	Gulati K
title	Nanoengineered drug-releasing Ti wires as an alternative for local delivery of chemotherapeutics in the brain
title_short	Nanoengineered drug-releasing Ti wires as an alternative for local delivery of chemotherapeutics in the brain
title_full	Nanoengineered drug-releasing Ti wires as an alternative for local delivery of chemotherapeutics in the brain
title_fullStr	Nanoengineered drug-releasing Ti wires as an alternative for local delivery of chemotherapeutics in the brain
title_full_unstemmed	Nanoengineered drug-releasing Ti wires as an alternative for local delivery of chemotherapeutics in the brain
title_sort	nanoengineered drug-releasing ti wires as an alternative for local delivery of chemotherapeutics in the brain
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/e60df70c0528473a8203a0be612b4a94
work_keys_str_mv	AT gulatik nanoengineereddrugreleasingtiwiresasanalternativeforlocaldeliveryofchemotherapeuticsinthebrain AT sinnawm nanoengineereddrugreleasingtiwiresasanalternativeforlocaldeliveryofchemotherapeuticsinthebrain AT losicd nanoengineereddrugreleasingtiwiresasanalternativeforlocaldeliveryofchemotherapeuticsinthebrain
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spelling	oai:doaj.org-article:e60df70c0528473a8203a0be612b4a942021-12-02T02:42:05ZNanoengineered drug-releasing Ti wires as an alternative for local delivery of chemotherapeutics in the brain1176-91141178-2013https://doaj.org/article/e60df70c0528473a8203a0be612b4a942012-04-01T00:00:00Zhttp://www.dovepress.com/nanoengineered-drug-releasing-ti-wires-as-an-alternative-for-local-del-a9736https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Karan Gulati1,2, Moom Sinn Aw1, Dusan Losic1,21Ian Wark Research Institute, The University of South Australia, Adelaide, SA, Australia; 2School of Chemical Engineering, The University of Adelaide, Adelaide, SA, AustraliaAbstract: The blood&ndash;brain barrier (BBB) blocks the passage of active molecules from the blood which makes drug delivery to the brain a challenging problem. Oral drug delivery using chemically modified drugs to enhance their transport properties or remove the blocking of drug transport across the BBB is explored as a common approach to address these problems, but with limited success. Local delivery of drugs directly to the brain interstitium using implants such as polymeric wafers, gels, and catheters has been recognized as a promising alternative particularly for the treatment of brain cancer (glioma) and neurodegenerative disorders. The aim of this study was to introduce a new solution by engineering a drug-releasing implant for local drug delivery in the brain, based on titanium (Ti) wires with titania nanotube (TNT) arrays on their surfaces. Drug loading and drug release characteristics of this system were explored using two drugs commonly used in oral brain therapy: dopamine (DOPA), a neurotransmitter agent; and doxorubicin (DOXO), an anticancer drug. Results showed that TNT/Ti wires could provide a considerable amount of drugs (&gt;170 &micro;g to 1000 &micro;g) with desirable release kinetics and controllable release time (1 to several weeks) and proved their feasibility for use as drug-releasing implants for local drug delivery in the brain.Purpose: In this report, a new drug-releasing platform in the form of nanoengineered Ti wires with TNT arrays is proposed as an alternative for local delivery of chemotherapeutics in the brain to bypass the BBB. To prove this concept, drug loading and release characteristics of two drugs important for brain therapy (the neurotransmitter DOPA and the anticancer drug DOXO) were explored.Methods: Titania nanotube arrays on the surface of Ti wires (TNT/Ti) were fabricated using a simple anodization process, followed by separate loading of two drugs (DOPA and DOXO) inside the nanotube structures. The loading and in vitro release characteristics of prepared TNT/Ti implants were examined using thermogravimetric analysis (TGA) UV-Vis spectroscopy.Results: Scanning electron microscopy studies confirmed that well-ordered, vertically aligned, densely packed nanotube arrays with an average diameter of 170 nm and length 70 &micro;m were formed on the surface of TNT/Ti wires. TGA results showed a total drug loading of 170 &micro;g and 1200 &micro;g inside the TNTs for DOPA and DOXO respectively. Two-phase drug release behavior was observed including a fast release (burst) for the first 6 hours and a prolonged slow release phase for 8 days, both with acceptable dosage and desirable release kinetics. The physical, structural, loading and release characteristics of prepared TNT/Ti implants showed several advantages in comparison with existing and clinically proved brain implants.Conclusion: Our results confirmed that TNT/Ti wires can be successfully employed as a suitable platform to release neurotransmitters such as DOPA and anticancer drugs such as DOXO. Hence, they are a feasible alternative as drug-releasing implants for local drug delivery in the brain to combat neurodegenerative disorders or brain tumors.Keywords: titania nanotubes, brain implants, local drug delivery, dopamine, doxorubicinGulati KSinn Aw MLosic DDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 2069-2076 (2012)

Nanoengineered drug-releasing Ti wires as an alternative for local delivery of chemotherapeutics in the brain

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