Autor(es)

Kai, Karen Cristina ; Borges, Roger ; Pedroni, Ana Clara Fagundes ; Pelosine, Agatha Maria ; da Cunha, Marcelo Rodrigues ; Marques, Marcia Martins ; de Araujo, Daniele Ribeiro ; Marchi, Juliana

• Tipo de documento: Artigo Científico
• Fonte: BIOMATERIALS ADVANCES; v. 164, p. 14-pg., 2024-08-01.

Resumo

Osteomyelitis is an inflammation of bone tissue usually caused by pyogenic bacteria. The most recurrent clinical approach consists of bone debridement followed by parenteral administration of antibiotics. However, systemic antibiotic treatment has limitations regarding absorption rate and bioavailability over time. The main challenge of osteomyelitis treatment consists of coupling the persistent infection treatment with the regeneration of the bone debrided. In this work, we developed an injectable drug delivery system based on poloxamer 407 hydrogel containing undoped Mg, Zn-doped tricalcium phosphate (beta-TCP), and teicoplanin, a broad-spectrum antibiotic. We evaluated how the addition of teicoplanin and beta-TCP affected the micellization, gelation, particle size, and surface charge of the hydrogel. Later, we studied the hydrogel degradation and drug delivery kinetics. Finally, the bactericidal, biocompatibility, and osteogenic properties were evaluated through in vitro studies and confirmed by in vivo Wistar rat models. Teicoplanin was found to be encapsulated in the corona portions of the hydrogel micelles, yielding a bigger hydrodynamics radius. The encapsulated teicoplanin showed a sustained release over the evaluated period, enough to trigger antibacterial properties against Gram-positive bacteria. Besides, the formulations were biocompatible and showed bone healing ability and osteogenic properties. Finally, in vivo studies confirmed that the proposed locally injected formulations yielded osteomyelitis treatment with superior outcomes than parenteral administration while promoting bone regeneration. In conclusion, the presented formulations are promising drug delivery systems for osteomyelitis treatment and deserve further technological improvements. (AU)

• Processo FAPESP: 13/11534-6 - Desenvolvimento de sistema carreador a base de poloxamer incorporado com beta-fosfato tricálcico dopado com magnésio e/ou zinco e teicoplanina visando o tratamento da osteomielite associada à reparação óssea
• Beneficiário: Juliana Marchi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/23803-9 - Incorporação de cerâmicas de fosfato tricálcico dopadas com magnésio e/ou zinco em matriz de hidrogel-fármaco para o tratamento da osteomielite associada à reparação óssea
• Beneficiário: Karen Cristina Kai
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/16512-9 - Desenvolvimento de um sistema carreador para liberação simultânea de fármaco e íons provenientes de vidros biocompatíveis a partir de uma matriz de hidrogel com os objetivos de auxiliar no tratamento de câncer ósseo e estimular a reparação óssea
• Beneficiário: Juliana Marchi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 20/00329-6 - Desenvolvimento de compósito multifuncional injetável para tratamento de câncer ósseo por hipertermia e braquiterapia associado à reparação óssea
• Beneficiário: Juliana Marchi
• Modalidade de apoio: Auxílio à Pesquisa - Regular