title: Aspartic acid-based modified PLGA-PEG nanoparticles for bone targeting: in vitro and in vivo evaluation.
abstract: Nanoparticles (NP) that target bone tissue were developed using PLGA-PEG (poly(lactic-co-glycolic acid)-polyethylene glycol) diblock copolymers and bone-targeting moieties based on aspartic acid, (Asp)(n(1,3)). These NP are expected to enable the transport of hydrophobic drugs. The molecular structures were examined by (1)H NMR or identified using mass spectrometry and Fourier transform infrared (FT-IR) spectra. The NP were prepared using the water miscible solvent displacement method, and their size characteristics were evaluated using transmission electron microscopy (TEM) and dynamic light scattering. The bone targeting potential of the NP was evaluated in vitro using hydroxyapatite affinity assays and in vivo using fluorescent imaging in zebrafish and rats. It was confirmed that the average particle size of the NP was <200 nm and that the dendritic Asp3 moiety of the PLGA-PEG-Asp3 NP exhibited the best apatite mineral binding ability. Preliminary findings in vivo bone affinity assays in zebrafish and rats indicated that the PLGA-PEG-ASP3 NP may display increased bone-targeting efficiency compared with other PLGA-PEG-based NP that lack a dendritic Asp3 moiety. These NP may act as a delivery system for hydrophobic drugs, warranting further evaluation of the treatment of bone disease.
authors: Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Orthopaedics, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Yin-Chih
authors: YC
authors: Fu
authors: Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors: Tzu-Fun
authors: TF
authors: Fu
authors: Department of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 807, Taiwan.
authors: Hung-Jen
authors: HJ
authors: Wang
authors: Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 807, Taiwan.
authors: Che-Wei
authors: CW
authors: Lin
authors: Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors: Gang-Hui
authors: GH
authors: Lee
authors: Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Shun-Cheng
authors: SC
authors: Wu
authors: Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 807, Taiwan. Electronic address: ckwang@kmu.edu.tw.
authors: Chih-Kuang
authors: CK
authors: Wang
mesh_terms: D000327:Adsorption; D000818:Animals; D001224:Aspartic Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D017886:Durapatite / Q000737:chemistry; D004705:Endocytosis / Q000187:drug effects; D007814:Larva / Q000187:drug effects; D008807:Mice, Inbred BALB C; D008903:Minerals / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011098:Polyglactin 910 / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D066244:Proton Magnetic Resonance Spectroscopy; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D055672:Static Electricity; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects; D015027:Zebrafish
chemical_list: D008903:Minerals; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D001224:Aspartic Acid; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D017886:Durapatite
keywords: Aspartic acid; Bone targeting; Drugs delivery; Nanoparticle; PLGA–PEG