Osteotropic nanoparticle-based drug delivery systems have been investigated as potential therapies for various skeletal diseases. These delivery systems are usually formulated by functionalizing the nanoparticle surfaces with bone-targeting ligands. Antibodies, proteins or peptide sequences
have shown promise as bone-targeting ligands; however, methods utilizing these targeting ligands suffer from many limitations including high production cost, protein or peptide instability, and unwanted immune response. These limitations can be minimized by using the osteotropic small molecule
approach because of the stability, ease of conjugation with polymeric nanoparticles, and low cost of small molecules. We, and others, have previously demonstrated that poly-aspartic acid sequencelinked biodegradable polymeric nanoparticles can interact specifically with mineralized tissue
in vitro, ex vivo, and in vivo. The hypothesis of this study is that single aspartic acid-linked nanoparticles can effectively interact with bone tissue specifically. In this study, we sought to identify the minimal aspartic acid residues stretch necessary for efficient
HA binding. We further sought to design a novel osteotropic nanoparticle-based drug delivery system using a single aspartic acid small molecule as the bone-targeting moiety.
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Targeted Drug Delivery;
Document Type: Research Article
Institute for Regenerative Engineering, University of Connecticut Health Center, School of Medicine, Farmington, CT 06030, United States
Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53705, United States
March 1, 2017
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