title: Poly(γ-benzyl-L-glutamate)-PEG-alendronate multivalent nanoparticles for bone targeting.
abstract: Hydroxyapatite (HAP), a highly specific component of bone tissue, is the main target in order to impart osteotropicity. Bone targeted nanoparticles can increase the strength of the interaction with HAP through multivalency and thus constitute a valuable strategy in the therapeutics of skeletal diseases. PBLG10k-b-PEG6k-alendronate nanoparticles (~ 75 nm) were prepared by a simple nanoprecipitation method. The calcium affinity (KCa(+2)=1.8 × 10(4)M(-1)) of these nanoparticles was evaluated using isothermal titration calorimetry. The multivalent interaction with HAP surfaces (KHAP) was studied by fluorescence and was estimated to be 1.1 × 10(10)M(-1), which is more than 4000 times stronger than the reported monovalent interaction between alendronate and HAP surfaces. Molecular modeling suggests that the number of binding sites available at the HAP surface is in large excess than what is required for the whole surface coverage by alendronate decorated nanoparticles. The lower calcium affinity of these nanoparticles than for HAP allows calcium bound nanoparticles to interact with HAP, which yields a deeper understanding of bone targeted carriers and could potentially improve their bone targeting properties.
authors.affiliation: Univ. Paris Sud, UMR CNRS 8612, Institut Galien, 92296 Châtenay-Malabry Cedex, France. Electronic address: laura.de-miguel@u-psud.fr.
authors.forename: Laura
authors.initials: L
authors.lastname: de Miguel
authors.affiliation: Univ. Paris Sud, UMR CNRS 8612, Institut Galien, 92296 Châtenay-Malabry Cedex, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Noiray
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Centre de Recherche de Gif-sur-Yvette, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
authors.forename: Georgiana
authors.initials: G
authors.lastname: Surpateanu
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Centre de Recherche de Gif-sur-Yvette, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
authors.forename: Bogdan I
authors.initials: BI
authors.lastname: Iorga
authors.affiliation: Univ. Paris Sud, UMR CNRS 8612, Institut Galien, 92296 Châtenay-Malabry Cedex, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Ponchel
mesh_terms: D019386:Alendronate / Q000737:chemistry*; D050071:Bone Density Conservation Agents / Q000737:chemistry*; D001842:Bone and Bones; D016503:Drug Delivery Systems; D017886:Durapatite / Q000737:chemistry; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D050071:Bone Density Conservation Agents; C003172:poly-gamma-benzyl-L-glutamate; D011099:Polyglutamic Acid; D011092:Polyethylene Glycols; D017886:Durapatite; D019386:Alendronate
keywords: (1)H NMR; ATR; Adsorption; BLG-NCA; Bone targeting; CDCl(3); CF3COOK; COOH; DCC; DCTB; DEE; DMF; DMSO; DPn; EtOH; FITC; HAP; ITC; Isothermal titration calorimetry; MALDI-TOF; MeO-PEG5k-NH2; MeOH; N,N′-dicyclohexylcarbodiimide; N-carboxylic anhydride; N-hydroxysuccinimide; NCA; NHS; NMR; Nanoparticles; PBLG; PBS; PEG; TEA; TEM; TFA; THF; UV; attenuated total reflection; benzyl; bnz; carboxylic acid; degree of polymerization; deuterated chloroform; diethyl ether; dimethyl sulfoxide; dimethylformamide; ethanol; fluorescein isothiocyanate; hydroxyapatite; isothermal titration calorimetry; matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; methanol; nuclear magnetic resonance; phosphate buffer saline; poly(γ-benzyl-l-glutamate); polyethylene glycol; potassium trifluoroacetate; proton nuclear magnetic resonance; tetrahydrofuran; trans-2-[3-(4-tert-butylphenyl)-2-methyl-2-propenylidene]malonitrile; transmission electron microscopy; triethylamine; trifluoroacetic acid; ultraviolet; α-methoxy-ω-amino poly(ethylene glycol)5000, NHSPEG6k-NHS, α,ω-Bis-N-hydroxysuccinimide-poly(ethylene glycol)6000; γ-benzyl-l-glutamate-N-carboxylic anhydride