Synthesis and characterization of surface-modified PBLG nanoparticles for bone targeting: in vitro and in vivo evaluations
Autor: | İpek Özcan, Gilles Ponchel, Tamer Güneri, Özgen Özer, Kawthar Bouchemal, Freimar Segura-Sánchez |
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Rok vydání: | 2010 |
Předmět: |
Chemistry
Surface Properties technology industry and agriculture Pharmaceutical Science Nanoparticle Isothermal titration calorimetry Polyethylene glycol In Vitro Techniques Bone and Bones Rats chemistry.chemical_compound Drug Delivery Systems Polymerization Microscopy Electron Transmission Polyglutamic Acid In vivo PEG ratio Drug delivery PEGylation Organic chemistry Animals Nanoparticles Fluorescein-5-isothiocyanate Nuclear chemistry |
Zdroj: | Journal of pharmaceutical sciences. 100(11) |
ISSN: | 1520-6017 |
Popis: | In this study, poly(γ-benzyl-l-glutamate) (PBLG) polypeptide derivatives were synthesized by ring-opening polymerization of amino acid N-carboxyanhydride using selected amine-terminated initiators. Alendronate, a targeting moiety that has a strong affinity for bone, was conjugated to PBLG. Monomethoxy polyethylene glycol (PEG) was used for a hydrophilic layer on the surface of the nanoparticles (NPs) to avoid reticuloendothelial system uptake. NPs were prepared by nanoprecipitation technique not only for PBLG or PBLG–PEG but also for composite polymers with different ratios. Fluorescein isothiocyanate would be attached to the NPs as a labeling agent. The size and morphology of NPs were evaluated by dynamic laser light scattering and transmission electron microscopy, and were found to be in a useful range (less than 80 nm) for bone-targeted drug delivery. In addition, the PEGylation of NPs was supported by isothermal titration calorimetry analysis. The bone-targeting potential of NPs was evaluated in vitro by calcium binding and hydroxyapatite affinity assays, and in vivo by fluorescent imaging experiments on rats. The targeted NPs showed bright fluorescent labeling in femur tissue. These results demonstrated the possibility of optimized NPs prepared with new PBLG derivatives to accumulate in bone successfully. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4877–4887, 2011 |
Databáze: | OpenAIRE |
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