title: Release of bioactive BMP from dextran-derived microspheres: a novel delivery concept.
abstract: Recent developments of biotechnology have produced a great variety of protein and bioactive drugs. For these drugs to be used therapeutically, suitable drug delivery systems have become increasingly essential. Dextran-derived biomaterials have been considered to be compatible matrices for protein and bioactive drugs because of their hydrophilic properties and ability to control drug dissolution and permeability. A novel class of dextran-glycidylmethacrylate (Dex-GMA)/poly(ethylene glycol) (PEG) microspheres were designed and synthesized by polymerization of Dex-GMA emulsified in an aqueous PEG solution. Dex-GMA was prepared by substituting the hydroxyl groups in Dex by GMA. The drug loading and in vitro drug release was evaluated by routine procedure and the biological activity of BMP-loaded microspheres was studied by experimental cytology methods. Recombinant human bone morphogenetic protein-2 (rhBMP-2) were entrapped in dextran-derived microspheres quantitatively and with full preservation of their biological activity. In vitro release kinetics indicated that dextran-derived microspheres could retain rhBMP-2 in a variable manner depending on the preparation and degradation of the microspheres. The release profiles of rhBMP-2 from microspheres as a function of time showed that rhBMP-2 releasing kinetics in vitro fitted to first-order and Higuchi equations. The release profile in vitro was in accord with two phases kinetics law and more than 60% drug were released during 20 days. Cytology studies showed rhBMP-2 microspheres have good biological effects on cultured periodontal ligament cells, and could achieve a longer action time than concentration of rhBMP-2 solution. These properties make those microspheres interesting osteo-conductive BMP carriers, allowing to decrease the amount of implanted factor required for tissue regeneration.
authors.affiliation: Department of Periodontology and Mucosal Diseases, College of Stomatology, The Fourth Military Medical University, 145th Chang-le Road, Xi'an 710032, Shaanxi, China. cfmsunhh@fmmu.edu.cn
authors.forename: Fa-ming
authors.initials: FM
authors.lastname: Chen
authors.forename: Zhi-fen
authors.initials: ZF
authors.lastname: Wu
authors.forename: Hai-hua
authors.initials: HH
authors.lastname: Sun
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.forename: Su-ning
authors.initials: SN
authors.lastname: Xin
authors.forename: Qin-tao
authors.initials: QT
authors.lastname: Wang
authors.forename: Guang-ying
authors.initials: GY
authors.lastname: Dong
authors.forename: Zhi-wei
authors.initials: ZW
authors.lastname: Ma
authors.forename: Sha
authors.initials: S
authors.lastname: Huang
authors.forename: Yong-jie
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000737:chemistry* / Q000494:pharmacology; D001861:Bone Regeneration; D002478:Cells, Cultured; D003911:Dextrans / Q000737:chemistry*; D004337:Drug Carriers; D004339:Drug Compounding; D004852:Epoxy Compounds / Q000737:chemistry; D006801:Humans; D008689:Methacrylates / Q000737:chemistry; D008863:Microspheres; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D053495:Osteopontin; D010513:Periodontal Ligament / Q000187:drug effects / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry* / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D003911:Dextrans; D004337:Drug Carriers; D004852:Epoxy Compounds; D008689:Methacrylates; D011994:Recombinant Proteins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D053495:Osteopontin; D011092:Polyethylene Glycols; D000469:Alkaline Phosphatase; C007870:glycidyl methacrylate