Biomaterials
Department of Chemistry, University of Kentucky, Lexington, KY 40506-0055, United States.
Published: April 2013
The objective of this work was to demonstrate the bioactivity of parathyroid hormone (1-34) (PTH) delivered through a single molecule of bisphosphonate to improve tissue/cell interactions. Bifunctional hydrazine-bisphosphonates (HBPs) with varying length and lipophilicity were used as a drug delivery vehicle. PTH was oxidized with periodate treatment to obtain an N-terminal aldehyde that was then conjugated to HBPs. The toxicity and apoptotic properties of HBPs and HBP-PTH conjugates were studied with macrophages (RAW 264.7). It was found that one of the HBPs had significant apoptotic characteristics similar to alendronate, which is a widely prescribed drug in the treatment of osteoporosis. The improved binding affinity of PTH following conjugation to HBP was determined using a hydroxyapatite binding assay. The amount of PTH delivered to bone through HBPs was not affected by the length or lipophilicity of the HBPs. Furthermore, the improved bioactivity of PTH delivered to bone through HBPs, in comparison to adsorbed PTH, was demonstrated by quantifying the cAMP produced by pre-osteoblastic (MC3T3-E1) cells in response to PTH. The delivery of bioactive PTH to bone tissue by HBP conjugation demonstrates the potential use of HBPs in delivering therapeutic macromolecules to bone for the treatment of several skeletal diseases.
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http://dx.doi.org/10.1016/j.biomaterials.2013.01.059 | DOI Listing |
Small Methods
October 2024
Department of Orthopedic Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, China.
Human parathyroid hormone (1-34) (PTH) exhibits osteoanabolic and osteocatabolic effects, with shorter plasma exposure times favoring bone formation. Subcutaneous injection (SCI) is the conventional delivery route for PTH but faces low delivery efficiency due to limited passive diffusion and the obstruction of the vascular endothelial barrier, leading to prolonged drug exposure times and reduced osteoanabolic effects. In this work, a microcurrent delivery system (MDS) based on multimicrochannel microneedle arrays (MMAs) is proposed, achieving high efficiency and safety for PTH transdermal delivery.
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Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology Cambridge Massachusetts USA.
Drug-carrying nanoparticles are a promising strategy to deliver therapeutics into the brain, but their translation requires better characterization of interactions between nanomaterials and endothelial cells of the blood-brain barrier (BBB). Here, we use a library of 18 layer-by-layer electrostatically assembled nanoparticles (NPs) to independently assess the impact of NP core and surface materials on in vitro uptake, transport, and intracellular trafficking in brain endothelial cells. We demonstrate that NP core stiffness determines the magnitude of transport, while surface chemistry directs intracellular trafficking.
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First Department of Medicine, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Ulmenweg 18, 91054 Erlangen, Germany.
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Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
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Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
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