Use of Anodized Titanium in Drug Delivery Applications

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0951-E12-28

Use of Anodized Titanium in Drug Delivery Applications Chang Yao, Ganesan Balasundaram, and Thomas Webster Brown University, Providence, RI, 02912

ABSTRACT One approach to improve the performance of current titanium implants is to create nanostructures via surface modification. Anodization is known to produce nanotubular structures on titanium surfaces when using fluorine containing solutions. Previous studies revealed enhanced osteoblast (bone-forming cell) adhesion and calcium deposition on anodized titanium possessing nanotubular structures compared to unanodized titanium. Moreover, it was found that protein adsorption (specifically, vitronectin and fibronectin) prior to cell adhesion increased on anodized compared to unanodized samples. These results all indicate that anodized titanium would be a good candidate for novel orthopedic implants. The nanotubes created by anodization have an inner diameter from 40 to 100 nm and a depth of a few hundred nanometers. In the present study, the drug delivery capability of such nanotubular structures was further characterized. Three different model drugs were tested: immunoglobulin G for foreign body response, bone morphogenetic protein active fragment for new bone growth, and penicillin/streptomycin for antimicrobial. First, these proteins were allowed to adsorb onto substrates for 24 h under room temperature. Then, the substrates with absorbed proteins were rinsed and transferred to new buffer solution kept at 37 °C. Buffer solution was collected and changed everyday. Finally, protein release from each substrate was measured using a commercial BCA assay kit. Results showed decreased immunoglobulin G adsorption, increased bone morphogenetic protein and penicillin/streptomycin adsorption on anodized titanium compared to unanodized ones. The release behavior of each protein on anodized and unanodized titanium is also studied. INTRODUCTION In a previous study, the cytocompatibility of anodized titania nanotube arrays was characterized and showed enhanced osteoblast (bone-forming cell) functions on such anodized titanium compared to untreated titanium [1]. Besides mimicking nanofeatures of bone, these titania nanotube arrays could potentially be a matrix for various therapeutic induction and thus lead to their controlled release. As a first step, the loading and release behavior of several model drugs like immunoglobulin G (IgG) [2], bone morphogenetic protein (BMP) active fragment [3, 4], and penicillin /streptomycin (P/S) [5] on these surfaces were studied to test the possibility of using such titania nanotube arrays for therapeutic drug delivery in the present study. Specifically, immunoglobulin G is a model drug for foreign body response, bone morphogenetic protein active fragment for new bone growth, and penicillin/streptomycin for antimicrobial. Solutions of these model drugs were adsorbed onto unanodized and anodized samples and then released to fresh buffer solutions changed every day. Eluted drug amounts up to five days were analyzed using a commercial p