title: Supramolecular assemblies of histidinylated β-cyclodextrin for enhanced oligopeptide delivery into osteoclast precursors.
abstract: Much attention has been given to the problem of drug delivery through the cell membrane in order to treat and manage bone diseases recently. The aim of this study was to develop nanoparticles made of amino- and histidinyl-modified amphiphilic β-cyclodextrins (β-CDs) entrapping osteoclast inhibitor, a hydrophobic oligopeptides drug, across the membrane of bone marrow-derived macrophages (BMMs). Drug-loaded β-CDs nanoparticles (NPs) were prepared by the emulsion solvent evaporation technique and fully characterized for size, zeta potential, and entrapment efficiency. Spherical NPs displaying a hydrodynamic radius of about 295 nm which did not change upon storage as an aqueous dispersion, a positive zeta potential, and entrapment efficiency of drug very close to 98% were produced. Flow cytometry and spectrofluorimetry analysis indicated that the model drug itself was not taken up by the BMMs; however, NP systems underwent significant cellular uptake. In particular, histidinyl group-modified CD (β-CD-H) NPs were taken up more efficiently than amino group-modified (β-CD-A) ones. Cellular uptake mechanism study demonstrated that the permeability of drug-loaded NPs across the membrane of BMMs is probably due to macropinocytosis pathway. Cell viability studies showed that both β-CD-A and β-CD-H exhibited no significant cytotoxicity up to 1.0 mg/ml against the cells. These results highlight the developed β-CD-H NPs have great potential in safely and effectively delivering osteoclast inhibitors and other therapeutic agents toward bone disease.
authors.affiliation: a State Key Laboratory of Materials-Oriented Chemical Engineering , Nanjing Tech University , Nanjing , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: a State Key Laboratory of Materials-Oriented Chemical Engineering , Nanjing Tech University , Nanjing , China.
authors.forename: Xuejin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: a State Key Laboratory of Materials-Oriented Chemical Engineering , Nanjing Tech University , Nanjing , China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: a State Key Laboratory of Materials-Oriented Chemical Engineering , Nanjing Tech University , Nanjing , China.|b Biopolymer Materials Laboratory, Department of Light Industry , Nanjing Tech University , Nanjing , China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.affiliation: a State Key Laboratory of Materials-Oriented Chemical Engineering , Nanjing Tech University , Nanjing , China.|b Biopolymer Materials Laboratory, Department of Light Industry , Nanjing Tech University , Nanjing , China.
authors.forename: Bo
authors.initials: B
authors.lastname: Chi
mesh_terms: D000818:Animals; D001692:Biological Transport; D001854:Bone Marrow Cells / Q000166:cytology; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D006639:Histidine / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010316:Particle Size; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000633:toxicity
chemical_list: D004337:Drug Carriers; D009842:Oligopeptides; D047392:beta-Cyclodextrins; D006639:Histidine
keywords: Cyclodextrins; cell penetration; cellular uptake; macropinocytosis; membrane; osteoclast inhibitor