Abstract
Bone tissue inflammation, osteomyelitis, is commonly caused by bacterial invasion and requires prolonged antibiotic therapy for weeks or months. Thus, the aim of this study was to develop novel silica-polymer local bone antibiotic delivery systems characterized by a sustained release of ciprofloxacin (CIP) which remain active against Staphylococcus aureus for a few weeks, and do not have a toxic effect towards human osteoblasts. Four formulations composed of ethylcellulose (EC), polydimethylsiloxane (PDMS), freeze-dried CIP, and CIP-adsorbed mesoporous silica materials (MCM-41-CIP) were prepared via solvent-evaporation blending method. All obtained composites were characterized in terms of molecular structure, morphological, and structural properties by using Fourier Transform Infrared Spectroscopy (FTIR), scanning electron microscopy equipped with energy-dispersive X-ray spectroscopy (SEM/EDX), and X-ray diffraction (XRD), thermal stability by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), and in vitro antibiotic release. The antibacterial activity against Staphylococcus aureus (ATCC 6538) as well as the in vitro cytocompatibility to human osteoblasts of obtained composites were also examined. Physicochemical results confirmed the presence of particular components (FTIR), formation of continuous polymer phase onto the surface of freeze-dried CIP or MCM-41-CIP (SEM/EDX), and semi-crystalline (composites containing freeze-dried CIP) or amorphous (composites containing MCM-41-CIP) structure (XRD). TGA and DSC analysis indicated the high thermal stability of CIP adsorbed onto the MCM-41, and higher after MCM-41-CIP coating with polymer blend. The release study revealed the significant reduction in initial burst of CIP for the composites which contained MCM-41-CIP instead of freeze-dried CIP. These composites were also characterized by the 30-day activity against S. aureus and the highest cytocompatibility to human osteoblasts in vitro.
Highlights
IntroductionBone fracture, or trauma may lead to severe bone inflammation such as osteomyelitis [1]
Surgical site infection, bone fracture, or trauma may lead to severe bone inflammation such as osteomyelitis [1]
Local bone antibiotic delivery systems (LBADS) have gained an increasing interest in the treatment of bone tissue infections, as an alternative method to the systemic therapy [3,4], that provide the release of antibiotics in controlled and sustained manner directly in infected bone site
Summary
Bone fracture, or trauma may lead to severe bone inflammation such as osteomyelitis [1]. Treatment with systemic delivery of antibiotics usually lasts from 4 to 6 weeks, and requires an administration of high dosages to achieve a sufficient concentration at the site of infection. It may be unachievable in patients with poorly vascularized infected tissue and osteonecrosis, which are common symptoms accompanying osteomyelitis [2]. The maintenance of antibiotics at high concentrations in bone tissue for a long time may lead to significant impairment of bone cells functions or cytotoxic effect [5,6]. The greatest challenge for LBADS is to provide the antibiotic at effective, bactericidal levels which are not toxic to human tissues
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