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Int J Pharm ; 582: 119322, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32298742

RESUMO

Infection and resulting bone defects caused by Staphylococcus aureus is one of the major issues in orthopaedic surgeries. Vancomycin hydrochloride (VaH) is largely used to manage these events. Here, a human derived bone paste supplemented with biopolymer microcarriers for VaH sustained delivery to merge osteoinductive and antimicrobial actions is described. In detail, different emulsion formulations were tested to fabricate micro-carriers of poly-lactic-co-glycolic acid (PLGA) and hydroxyapatite (HA) by a proprietary technology (named Supercritical Emulsion Extraction). These carriers (mean size 827 ± 68 µm; loading 47 mgVaH/gPLGA) were assembled with human demineralized bone matrix (DBM) to obtain an antimicrobial bone paste system (250 mg/0.5 cm3 w/v, carrier/DBM). Release profiles in PBS indicated a daily drug average release of about 4 µg/mL over two weeks. This concentration was close to the minimum inhibitory concentration and able to effectively inhibit the S. aureus growth in our experimental sets. Carriers cytotoxicity tests showed absence of adverse effects on cell viability at the concentrations used for paste assembly. This approach points toward the potential of the DBM-carrier-antibiotic system in hampering the bacterial growth with accurately controlled antibiotic release and opens perspectives on functional bone paste with PLGA carriers for the controlled release of bioactive molecules.


Assuntos
Antibacterianos/farmacologia , Materiais Biomiméticos , Matriz Óssea/química , Portadores de Fármacos , Durapatita/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Staphylococcus aureus/efeitos dos fármacos , Vancomicina/farmacologia , Antibacterianos/química , Antibacterianos/toxicidade , Técnica de Desmineralização Óssea , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Preparações de Ação Retardada , Composição de Medicamentos , Liberação Controlada de Fármacos , Durapatita/toxicidade , Humanos , Cinética , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/toxicidade , Staphylococcus aureus/crescimento & desenvolvimento , Vancomicina/química , Vancomicina/toxicidade
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