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Tricalcium phosphate-loaded injectable hydrogel as a promising osteogenic and bactericidal teicoplanin-delivery system for osteomyelitis treatment: An in vitro and in vivo investigation

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Author(s):
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
Total Authors: 8
Document type: Journal article
Source: BIOMATERIALS ADVANCES; v. 164, p. 14-pg., 2024-08-01.
Abstract

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)

FAPESP's process: 13/11534-6 - Development of a carrier-based poloxamer system incorporated with beta-tricalcium phosphate doped with magnesium and/or zinc and teicoplanin aiming the osteomyelitis treatment associated with bone repair
Grantee:Juliana Marchi
Support Opportunities: Regular Research Grants
FAPESP's process: 12/23803-9 - Incorporation of magnesium and/or zinc doped-tricalcium phosphate ceramics doped in a hydrogel-drug matrix for osteomyelitis treatment associated with bone repairment
Grantee:Karen Cristina Kai
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 16/16512-9 - Development of a hydrogel-based delivery system for release of biocompatible glasses ions and drug as support in treatment of bone cancer and subsequent bone regeneration
Grantee:Juliana Marchi
Support Opportunities: Regular Research Grants
FAPESP's process: 20/00329-6 - Development of a multifunctional injectable composite aiming bone cancer treatment through hyperthermia and brachytherapy allied with bone repair
Grantee:Juliana Marchi
Support Opportunities: Regular Research Grants