期刊
JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
卷 18, 期 4, 页码 2310-2317出版社
AMER SCIENTIFIC PUBLISHERS
DOI: 10.1166/jnn.2018.14311
关键词
Osteoarthritis; Musculoskeletal Tissue; Targeting Ligands; Targeted Drug Delivery; Nanomedicine
类别
资金
- State of Connecticut Stem Cell Research Foundation [13-SCA-UCHC-01]
- Connecticut Institute for Clinical and Translational Science Start-up Funds
Osteoarthritis is a severe and debilitating joint disease, which is characterized as results from damage and degeneration of the articular cartilage of the joint surfaces. The incidence of osteoarthritis is growing increasingly high while current treatment methods remain suboptimal. The major issue for current osteoarthritic medications is that patients frequently experience adverse, nonspecific side effects that are not a direct result of the specific pharmacological action of the drug. The treatment processes could be made more effective, safe, and comfortable if it were possible to deliver the drugs specifically to cartilage tissue. Therefore, developing site-specific and controlled drug release delivery systems is needed for overcoming the aforementioned issues. We have developed a poly(lactic-co-glycolic acid) (PLGA)-based nanoscale drug delivery system based on a short cartilage-targeting peptide sequence: WYRGRL. Nanoparticles (NPs) made of methoxypoly(ethylene glycol) (PEG)-PLGA and maleimide-PEG-PLGA were prepared using a water-in-oil-in-water double emulsion and solvent evaporation method. Fluorescein isothiocyanate (FITC)-tagged WYRGRL peptide was then linked to the surface of the nanoparticles through the alkylation reaction between the sulfhydryl groups at the N-terminal of the peptide and the C=C double bond of maleimide at one end of the polymer chain to form thioether bonds. The conjugation of FITC-tagged WYRGRL peptide to PLGA NPs was confirmed by NMR technique. We further demonstrated that the novel delivery system binds very specifically to cartilage tissue in vitro and ex vivo. Given that biodegradable PLGA-based NPs have shown promise for drug delivery, they could be used for a positive advancement for treatments of osteoarthritic patients by creating a more effective treatment process that achieves healing results faster and with fewer deleterious side effects. Taken together, these promising results indicated that this nanoscale targeting drug delivery system was able to bind to cartilage tissue and might have a great potential for treating osteoarthritis.
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