Drug Deliverable, Self-assembled Rosette Nanotubes (RNTs) for Orthopedic Applications
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Drug Deliverable, Self-assembled Rosette Nanotubes (RNTs) for Orthopedic Applications Yupeng Chen1, 2*, Shang Song2*, Hicham Fenniri4 and Thomas J. Webster2, 3 1
Chemistry Department, 2Division of Engineering, 3Department of Orthopaedics, Brown University, Providence, 02912, RI, USA. 4 National Institute for Nanotechnology and Department of Chemistry, National Research Council and University of Alberta, Edmonton, AB T6G ZV4, CANADA. *Equal contribution to the present study.
ABSTRACT Rosette nanotubes (RNTs) are novel, biomimetic, synthetic, self-assembled drug delivery agents. Because of base stacking and hydrophobic interactions, the RNT hollow-tube structure can be used for incorporating drugs. Another advantage of using RNTs is their ability to be injected and become solid at body temperatures for orthopedic applications without the use of any external stimuli (such as UV light or crosslinking agents). The nano-features of RNTs create a favorable, biologically-inspired, cellular environment. In this study, methods to incorporate dexamethasone (DEX, a bone growth promoting drug) into RNTs were investigated. The drugloaded RNTs were characterized using Nuclear Magnetic Resonance (NMR), Diffusion Ordered Spectroscopy (DOSY) and Ultraviolet-visible Spectroscopy (UV-vis). Results showed that small molecular drugs with hydrophobic aromatic rings were incorporated into RNTs. Subsequent drug release experiments demonstrated that DEX was released from the RNTs and had a positive impact on osteoblast functions. Importantly, RNTs increased the total drug loading and was the highest when DEX was incorporated during the RNT self-assembly process. Such results demonstrated a possibility to incorporate drugs inside RNTs by self-assembly to delivery hydrophobic drugs or elongate drug release time. Thus, this study offered a novel drug delivery device that itself is bioactive and can be used to deliver a variety of drugs for various orthopedic applications. INTRODUCTION Bone tissue engineering is one of the earliest researched areas in all of tissue replacement. Since the first hip replacement surgery was conducted in 1923, various bone implants (such as for healing bone fractures, repairing defects and reconstructing joints) have been routinely inserted increasing the quality of life for millions of people [1]. So far, a variety of biomaterials have been investigated for bone implantation, such as conventional titanium and its alloys, micron gain sized ceramics (like hydroxylapatite, HA) and nano-smooth hydrogels (like poly
(lactic-co-glycolic acid)) [2~5]. However, current conventional implants display continual problems in these areas leading implant failure [6~7]. For example, they usually have insufficient initial bone growth on the surface of the implant and/or poor maintenance of healthy juxtaposed bone, which causes a lack or separation of bone growth surrounding the implant and eventually leads to bone loss, implant loosening, and failure of implantation. From October 1, 2005 to December 31, 2006, 51,34
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