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Characterization of drug-release kinetics in trabecular bone from titania nanotube implants

Authors Aw MS, Khalid KA, Gulati K, Atkins GJ, Pivonka P, Findlay DM, Losic D

Received 12 May 2012

Accepted for publication 21 June 2012

Published 12 September 2012 Volume 2012:7 Pages 4883—4892

DOI https://doi.org/10.2147/IJN.S33655

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Moom Sinn Aw,1 Kamarul A Khalid,2,3 Karan Gulati,1 Gerald J Atkins,2 Peter Pivonka,4 David M Findlay,2 Dusan Losic1

1School of Chemical Engineering, 2Discipline of Orthopaedics and Trauma, The University of Adelaide, Adelaide, SA, Australia; 3Department of Orthopaedics, Traumatology and Rehabilitation, Faculty of Medicine, International Islamic University Malaysia, Kuantan, Pahang, Malaysia; 4Engineering Computational Biology Group, School of Computer Science and Software Engineering, The University of Western Australia, Perth, WA, Australia

Purpose: The aim of this study was to investigate the application of the three-dimensional bone bioreactor for studying drug-release kinetics and distribution of drugs in the ex vivo cancellous bone environment, and to demonstrate the application of nanoengineered titanium (Ti) wires generated with titania nanotube (TNT) arrays as drug-releasing implants for local drug delivery
Methods: Nanoengineered Ti wires covered with a layer of TNT arrays implanted in bone were used as a drug-releasing implant. Viable bovine trabecular bone was used as the ex vivo bone substrate embedded with the implants and placed in the bone reactor. A hydrophilic fluorescent dye (rhodamine B) was used as the model drug, loaded inside the TNT–Ti implants, to monitor drug release and transport in trabecular bone. The distribution of released model drug in the bone was monitored throughout the bone structure, and concentration profiles at different vertical (0–5 mm) and horizontal (0–10 mm) distances from the implant surface were obtained at a range of release times from 1 hour to 5 days.
Results: Scanning electron microscopy confirmed that well-ordered, vertically aligned nanotube arrays were formed on the surface of prepared TNT–Ti wires. Thermogravimetric analysis proved loading of the model drug and fluorescence spectroscopy was used to show drug-release characteristics in-vitro. The drug release from implants inserted into bone ex vivo showed a consistent gradual release of model drug from the TNT–Ti implants, with a characteristic three-dimensional distribution into the surrounding bone, over a period of 5 days. The parameters including the flow rate of bone culture medium, differences in trabecular microarchitecture between bone samples, and mechanical loading were found to have the most significant influence on drug distribution in the bone.
Conclusion: These results demonstrate the utility of the Zetos™ system for ex vivo drug-release studies in bone, which can be applied to optimize the delivery of specific therapies and to assist in the design of new drug delivery systems. This method has the potential to provide new knowledge to understand drug distribution in the bone environment and to considerably improve existing technologies for local administration in bone, including solving some critical problems in bone therapy and orthopedic implants.

Keywords: local drug delivery, Zetos bone bioreactor, drug-releasing implant, drug diffusion

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