1. Calcium phosphate nanoparticles functionalized with alendronate-conjugated polyethylene glycol (PEG) for the treatment of bone metastasis.
- Author
-
Chu W, Huang Y, Yang C, Liao Y, Zhang X, Yan M, Cui S, and Zhao C
- Subjects
- Alendronate metabolism, Animals, Antimetabolites, Antineoplastic administration & dosage, Antimetabolites, Antineoplastic pharmacokinetics, Antimetabolites, Antineoplastic pharmacology, Bone Neoplasms secondary, Cell Line, Cell Line, Tumor, Cell Survival drug effects, Drug Carriers chemistry, Drug Delivery Systems, Durapatite metabolism, Female, Humans, Methotrexate pharmacokinetics, Methotrexate pharmacology, Mice, Nanoparticles, Photoelectron Spectroscopy, Polyethylene Glycols chemistry, Rats, Rats, Sprague-Dawley, Tissue Distribution, Alendronate chemistry, Bone Neoplasms drug therapy, Calcium Phosphates chemistry, Methotrexate administration & dosage
- Abstract
Because of the peculiarity of the bone microstructure, the uptake of chemotherapeutics often happens at non-targeted sites, which induces side effects. In order to solve this problem, we designed a bone-targeting drug delivery system that can release drug exclusively in the nidus of the bone. Alendronate (ALN), which has a high ability to target to hydroxyapatite, was used to fabricate double ALN-conjugated poly (ethylene glycol) 2000 material (ALN-PEG
2k -ALN). The ALN-PEG2k -ALN was characterized using1 H NMR and31 P NMR and FTIR. ALN-PEG2k -ALN-modified calcium phosphate nanoparticles (APA-CPNPs) with an ALN targeting moiety and hydrophilic poly (ethylene glycol) arms tiled on the surface was prepared for bone-targeted drug delivery. The distribution of ALN-PEG2k -ALN was tested by X-ray photoelectron spectroscopy. Isothermal titration calorimetry data indicated that similar to free ALN, both ALN-PEG2k -ALN and APA-CPNPs can bind to calcium ions. The bone-binding ability of APA-CPNPs was verified via ex vivo imaging of bone fragments. An in vitro release experiment demonstrated that APA-CPNPs can release drug faster in an acid environment than a neutral environment. Cell viability experiments indicated that blank APA-CPNPs possessed excellent biocompatibility with normal cells. Methotrexate (MTX) loaded APA-CPNPs have the same ability to inhibit cancer cells as free drug at high concentrations, while they are slightly weaker at low concentrations. All of these experiments verified the prospective application of APA-CPNPs as a bone-targeting drug delivery system., (Copyright © 2016 Elsevier B.V. All rights reserved.)- Published
- 2017
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