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 (ß-TCP), and teicoplanin, a broad-spectrum antibiotic. We evaluated how the addition of teicoplanin and ß-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.
Assuntos
Antibacterianos , Fosfatos de Cálcio , Hidrogéis , Osteogênese , Osteomielite , Ratos Wistar , Teicoplanina , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Animais , Fosfatos de Cálcio/química , Teicoplanina/administração & dosagem , Teicoplanina/farmacologia , Teicoplanina/química , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Antibacterianos/química , Ratos , Hidrogéis/química , Hidrogéis/administração & dosagem , Osteogênese/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Humanos , Staphylococcus aureus/efeitos dos fármacos , Poloxâmero/químicaRESUMO
Xyloglucans are water-soluble polysaccharides that serve as storage in cotyledonary tissues from seeds of Hymenaea courbaril among other Leguminosae. The use of xyloglucans is dependent on their solution properties. We now examine the influence of different times of extractions on its properties. Xyloglucans were obtained from milled and defatted cotyledons of H. courbaril by aqueous extraction at 25 degrees C for 0.25, 0.5, 1, 5, 15, 24, and 48 h. Composition data showed that increase in time lead to the increased protein contamination and arabinose content. Xyloglucans obtained with longer times of extraction had an average molar mass greater than those obtained with shorter times. The hydrodynamic radius and the radius of gyration also increased with the increase in the time of extraction. The ratio R(g)/R(h) was calculated and the values decreased slightly for increasing times of extraction. The effect of time also affected the viscosity which increased with the increase in time of extraction, and the longer ones probably contributing to the aggregation of xyloglucans.