title: Sustained release of small molecules from carbon nanotube-reinforced monetite calcium phosphate cement.
abstract: The interest in developing calcium phosphate cement (CPC) as a drug delivery system has risen because of its capability to achieve local and controlled treatment to the site of the bone disease. The purpose of this study was to investigate the release pattern of drug-carrying carboxylic acid-functionalized multi-walled carbon nanotube (MWCNT)-reinforced monetite (DCPA, CaHPO4)-based CPC. Z-Leu-Leu-Leu-al (MG132), a small peptide molecule inhibiting NF-κB-mediated osteoclastic resorption, was used as a model drug. MG132 was added into the cement during setting and released into the medium used to culture indicator cells. Significant cell death was observed in osteoblast MC3T3-E1 cells cultured in the medium incubated with MG132-loaded CPC; however, with the presence of MWCNTs in the cement, the toxic effect was not detectable. NF-κB activation was quantified using a NF-κB promoter-driving luciferase reporter in human embryonic kidney 293 cells. The medium collected after incubation with drug-incorporated CPC with or without MWCNT inhibited TNFα-induced NF-κB activation indicating that the effective amount of MG132 was released. CPC/drug complex showed a rapid release within 24h whereas incorporation of MWCNTs attenuated this burst release effect. In addition, suppression of TNFα-induced osteoclast differentiation in RAW 264.7 cell culture also confirmed the sustained release of MWCNT/CPC/drug. Our data demonstrated the drug delivery capability of this cement composite, which can potentially be used to carry therapeutic molecules to improve bone regeneration in conjunction with its fracture stabilizing function. Furthermore, it suggested a novel approach to lessen the burst release effect of the CPC-based drug delivery system by incorporating functionalized MWCNTs.
authors.affiliation: Department of Bioengineering, the University of Toledo, 2801 W Bancroft Street, Toledo, OH 43606, USA. Electronic address: boren.lin@utoledo.edu.
authors.forename: Boren
authors.initials: B
authors.lastname: Lin
authors.affiliation: Department of Mechanical, Industrial and Manufacturing Engineering, the University of Toledo, 2801 W Bancroft Street, Toledo, OH 43606, USA.
authors.forename: Huan
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Biological Sciences, the University of Toledo, 2801 W Bancroft Street, Toledo, OH 43606, USA.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Leaman
authors.affiliation: Department of Bioengineering, the University of Toledo, 2801 W Bancroft Street, Toledo, OH 43606, USA.
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Goel
authors.affiliation: Department of Bioengineering, the University of Toledo, 2801 W Bancroft Street, Toledo, OH 43606, USA.
authors.forename: Anand K
authors.initials: AK
authors.lastname: Agarwal
authors.affiliation: Department of Mechanical, Industrial and Manufacturing Engineering, the University of Toledo, 2801 W Bancroft Street, Toledo, OH 43606, USA.
authors.forename: Sarit B
authors.initials: SB
authors.lastname: Bhaduri
mesh_terms: D000818:Animals; D001843:Bone Cements; D002130:Calcium Phosphates / Q000737:chemistry*; D002460:Cell Line; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008855:Microscopy, Electron, Scanning; D016328:NF-kappa B / Q000235:genetics; D037742:Nanotubes, Carbon; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D001843:Bone Cements; D002130:Calcium Phosphates; D016328:NF-kappa B; D037742:Nanotubes, Carbon; C485829:calcium phosphate, dibasic, anhydrous
keywords: Bone regeneration; Calcium phosphate cement; Carbon nanotubes; Drug delivery; Osteoclastic inhibition