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1.
Acta Pharm ; 66(3): 373-85, 2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-27383886

RESUMO

Silicon-substituted calcium phosphate (Si-CaP) was developed in our laboratory as a biomaterial for delivery in bone tissue engineering. It was fabricated as a 3D-construct of scaffolds using chitosan-trisodium polyphosphate (TPP) cross-linked networks. In this study, heparin was covalently bonded to the residual -NH2 groups of chitosan on the scaffold applying carbodiimide chemistry. Bonded heparin was not leached away from scaffold surfaces upon vigorous washing or extended storage. Recombinant human bone morphogenetic protein 2 (rhBMP-2) was bound to conjugated scaffolds by ionic interactions between the negatively charged SO42- clusters of heparin and positively charged amino acids of rhBMP-2. The resulting scaffolds were inspected for bone regenerative capacity by subcutaneous implanting in rats. Histological observation and mineralization assay were performed after 4 weeks of implantation. Results from both in vitro and in vivo experiments suggest the potential of the developed scaffolds for bone tissue engineering applications in the future.


Assuntos
Anticoagulantes/administração & dosagem , Proteína Morfogenética Óssea 2/administração & dosagem , Regeneração Óssea/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/química , Sistemas de Liberação de Medicamentos , Heparina/administração & dosagem , Alicerces Teciduais/química , Animais , Anticoagulantes/efeitos adversos , Anticoagulantes/química , Anticoagulantes/farmacologia , Proteína Morfogenética Óssea 2/química , Proteína Morfogenética Óssea 2/genética , Proteína Morfogenética Óssea 2/farmacologia , Fosfatos de Cálcio/efeitos adversos , Fosfatos de Cálcio/química , Quitosana/efeitos adversos , Quitosana/química , Quitosana/metabolismo , Materiais Revestidos Biocompatíveis/efeitos adversos , Reagentes de Ligações Cruzadas/química , Sistemas de Liberação de Medicamentos/efeitos adversos , Liberação Controlada de Fármacos , Etildimetilaminopropil Carbodi-Imida/química , Heparina/efeitos adversos , Heparina/química , Humanos , Masculino , Polifosfatos/efeitos adversos , Polifosfatos/química , Polifosfatos/metabolismo , Ratos Wistar , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacologia , Silicones/efeitos adversos , Silicones/química , Solubilidade , Propriedades de Superfície , Alicerces Teciduais/efeitos adversos
2.
J Pharm Sci ; 101(8): 2870-82, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22674208

RESUMO

In this study, a new generation of bioactive glass ceramics were developed using the wet chemical method. The synthetic conditions were strictly controlled to obtain the materials of a nanometric scale. As evaluated by scanning electron microscopy, bone-like apatite layers were produced in large amounts and completely covered their surfaces after immersion in phosphate buffer saline. On the basis of X-ray diffraction, X-ray fluorescence, and Fourier transform infrared spectroscopy results, PO4³â» groups of hydroxyapatite (HA) were partially substituted by SiO44⁻ species. The defective chemical structures introduced provided materials that were more biologically active, compared with the parent HA. For effective treatment of infected bones, scaffolds containing the bioactive ceramics were prepared by chitosan cross-linking, and loaded with vancomycin (VCM). The drug-loaded scaffolds were not toxic to bone cells. About 75%-80% of the entrapped drug was released in a controlled pattern and the release was sustained over a 12-day period. The concentration of drug released was determined to be above 20 times the half maximal effective concentration of VCM on Staphylococcus aureus, and was sufficient for killing bacteria growing as biofilm. In summary, the synthesized bioceramics exhibited many of properties associated with an ideal material for implantable drug delivery system, and were suitable for testing the ability to cure bone diseases including osteomyelitis.


Assuntos
Antibacterianos/administração & dosagem , Substitutos Ósseos/química , Cerâmica/química , Sistemas de Liberação de Medicamentos/métodos , Osteomielite/tratamento farmacológico , Vancomicina/administração & dosagem , Animais , Antibacterianos/farmacologia , Substitutos Ósseos/síntese química , Osso e Ossos/citologia , Linhagem Celular , Sobrevivência Celular , Cerâmica/síntese química , Durapatita/química , Humanos , Ratos , Dióxido de Silício/química , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Vancomicina/farmacologia
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