title: Synthesis and characterization of surface-modified PBLG nanoparticles for bone targeting: in vitro and in vivo evaluations.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Ege University, 35100 Izmir, Turkey. ipek.ozcan@ege.edu.tr
authors.forename: Ipek
authors.initials: I
authors.lastname: Ozcan
authors.forename: Kawthar
authors.initials: K
authors.lastname: Bouchemal
authors.forename: Freimar
authors.initials: F
authors.lastname: Segura-Sánchez
authors.forename: Ozgen
authors.initials: O
authors.lastname: Ozer
authors.forename: Tamer
authors.initials: T
authors.lastname: Güneri
authors.forename: Gilles
authors.initials: G
authors.lastname: Ponchel
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000187:drug effects*; D016503:Drug Delivery Systems; D016650:Fluorescein-5-isothiocyanate; D066298:In Vitro Techniques; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D051381:Rats; D013499:Surface Properties
chemical_list: C003172:poly-gamma-benzyl-L-glutamate; D011099:Polyglutamic Acid; D016650:Fluorescein-5-isothiocyanate