Local co-delivery of rhBMP-2 and cathepsin K inhibitor L006235 in poly(d,l-lactide-co-glycolide) nanospheres.

Autor: Yu NY; Department of Orthopaedic Research & Biotechnology, Kids Research Institute at The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia.; Discipline of Paediatrics and Child Health, Faculty of Medicine, A27 University of Sydney, NSW, 2006, Australia., Fathi A; School of Chemical and Biomolecular Engineering, University of Sydney, NSW, 2006, Australia., Murphy CM; Department of Orthopaedic Research & Biotechnology, Kids Research Institute at The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia.; Discipline of Paediatrics and Child Health, Faculty of Medicine, A27 University of Sydney, NSW, 2006, Australia., Mikulec K; Department of Orthopaedic Research & Biotechnology, Kids Research Institute at The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia., Peacock L; Department of Orthopaedic Research & Biotechnology, Kids Research Institute at The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia., Cantrill LC; Discipline of Paediatrics and Child Health, Faculty of Medicine, A27 University of Sydney, NSW, 2006, Australia.; Microscopy Services, Kids Research Institute at The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia., Dehghani F; School of Chemical and Biomolecular Engineering, University of Sydney, NSW, 2006, Australia., Little DG; Department of Orthopaedic Research & Biotechnology, Kids Research Institute at The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia.; Discipline of Paediatrics and Child Health, Faculty of Medicine, A27 University of Sydney, NSW, 2006, Australia., Schindeler A; Department of Orthopaedic Research & Biotechnology, Kids Research Institute at The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia.; Discipline of Paediatrics and Child Health, Faculty of Medicine, A27 University of Sydney, NSW, 2006, Australia.
Jazyk: angličtina
Zdroj: Journal of biomedical materials research. Part B, Applied biomaterials [J Biomed Mater Res B Appl Biomater] 2017 Jan; Vol. 105 (1), pp. 136-144. Date of Electronic Publication: 2015 Oct 05.
DOI: 10.1002/jbm.b.33481
Abstrakt: Cathepsin K inhibitors (CKIs) are an emerging class of drugs that are potent antagonists of osteoclastic activity. We speculated that they may be beneficial in bone tissue engineering, where a stress shielded environment can lead to rapid resorption of new bone. Most CKIs require frequent dosing, so to achieve a sustained release we manufactured polymer nanoparticles encapsulating the CKI L006235 (CKI/nP). CKI/nP and the collagen matrices that were used to deliver them were characterized by electron microscopy and fluorescent confocal microscopy, and data indicated that the particles were evenly distributed throughout the collagen. Elution studies indicated a linear release of the inhibitor from the CKI/nP, with approximately 2% of the drug being released per day. In an in vivo study, mice were implanted with collagen scaffolds containing rhBMP-2 that were loaded with the CKI/nP. Measurement of bone volume (BV) by microCT showed no significant increase with CKI/nP incorporation, and other parameters similarly showed no statistical differences. Cell culture studies confirmed the activity of the drug, even at low concentrations. These data indicate that polymer nanoparticles are an effective method for sustained drug delivery of a CKI, however, this may not be readily translatable to substantively improved bone tissue engineering outcomes. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 136-144, 2017.
(© 2015 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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