title: Alendronate-decorated biodegradable polymeric micelles for potential bone-targeted delivery of vancomycin.
abstract: Osteomyelitis is a bone infection disease which is caused by bacteria or other germs, and could cause serious impact on the health and working capacity of the patients. Alendronate (ALN) can chelate strongly with the calcium ion of hydroxyapatite (HA) which is commonly used to treat osteoporosis. Nanomedicine has attracted a lot of attention in that the nano-sized carrier can deliver drug molecules to specific site of interest with the aid of targeting moiety and achieve sustained release, resulting in improved therapeutic effect and reduced side effect. In this study, micelles self-assembled from poly(lactic acid-co-glycolic acid)-block-poly(ethylene glycol)-alendronate (PLGA-PEG-ALN) copolymer were prepared for bone-targeted delivery of vancomycin (Van). The chemical structure of PLGA-PEG-ALN was confirmed by proton nuclear magnetic resonance ((1)H-NMR) spectroscopy. The formation of the nanoparticles was characterized by dynamic light scattering, transmission electronic microscopy as well as the critical micelle concentration measurement. Release profiles from the micelles revealed that the conjugation of ALN to the surface of micelle did not pose adverse effect on the drug-loading capacity and release behaviors. The cytotoxicity of Van-loaded PLGA-PEG-ALN micelles as well as the blank micelles was evaluated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay toward rat bone marrow stromal cells (rBMSCs) and human embryonic hepatocytes (L02 cells), and results showed that this Van-loaded micelle possesses appropriate cytotoxicity and is safe in the potential treatment of osteomyelitis. The in vitro affinity of PLGA-PEG-ALN micelles to the HA was also confirmed in vitro. The antibacterial effect of Van-loaded PLGA-PEG-ALN micelles was tested against Staphylococcus aureus (SA) which is the main pathogenic bacteria in osteomyelitis, and the results showed that the Van-loaded micelles can effectively inhibit the growth of SA. These results demonstrated that the PLGA-PEG-ALN micelles may be potentially used for the bone targeted delivery of Van.
authors.affiliation: a School of Chemistry, Chemical Engineering and Life Sciences , Wuhan University of Technology , Wuhan , Hubei 430070 , China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Cong
authors.forename: Changyun
authors.initials: C
authors.lastname: Quan
authors.forename: Meiqing
authors.initials: M
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: Huang
authors.forename: Guoquan
authors.initials: G
authors.lastname: Tong
authors.forename: Yihua
authors.initials: Y
authors.lastname: Yin
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiang
mesh_terms: D019386:Alendronate / Q000737:chemistry*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D001842:Bone and Bones / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D065546:Drug Liberation; D017886:Durapatite / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D019344:Lactic Acid / Q000737:chemistry*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008823:Micelles; D008826:Microbial Sensitivity Tests; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D014640:Vancomycin / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); D014640:Vancomycin; D017886:Durapatite; D019386:Alendronate
keywords: alendronate; bone-targeting; nanoparticles; osteomyelitis; vancomycin