Abstract
Bone infection is a feared complication for patients with surgically fixed bone fractures and local antibiotic delivery is important in prophylaxis and treatment of these infections. Recent studies indicated that Staphylococcus aureus can penetrate bone tissue through micron-sized canaliculi and evade systemic and currently available local antibiotic treatments. Targeting bacteria within the bone requires highly efficient delivery of antimicrobials to the infected bone tissue. In this work, a biodegradable microsphere carrier loaded with antibiotics and with specific affinity to bone mineral was developed. Two widely used antibiotics, i.e., Gentamicin-dioctyl sulfosuccinate (GM-AOT) and Ciprofloxacin (CF) were embedded in poly(ϵ-caprolactone) (PCL) microspheres fabricated by oil-in-water emulsion techniques with carboxylated poly(vinyl alcohol) (cPVA) as surfactant. The carboxylic acid groups present at the Poly(ϵ-caprolactone)/cPVA (PCL-cPVA) microsphere surface were functionalized with aspartic acid oligomers (ASP) granting bone targeting properties. We report on cPVA synthesis, microsphere formulation, and antibiotic loading of PCL/cPVA-ASP microspheres. Antibiotic loaded PCL/cPVA-ASP microspheres show sustained release of its antibiotic load and can inhibit bacterial growth in vitro for up to 6 days. PCL/cPVA-ASP microspheres show enhanced affinity to mineralized substrates compared to non-functionalized PCL/cPVA microspheres. These findings support further development of these bone targeting antibiotic carriers for potential treatment of persistent bone infections.
Highlights
In orthopedic surgery, osteomyelitis (OM) is a dreaded complication that can affect up to 27% of patients with bone fractures [1]
We previously reported on an antibiotic delivery system consisting of Alendronate (ALN) functionalized poly( -caprolactone) (PCL) microspheres in which hydrophobic Gentamicin-dioctyl sulfosuccinate (GM-AOT) was embedded in the PCL polymer matrix [18]
In this work we aimed to develop an oil/water (O/W) emulsion-based production of antibiotic loaded PCL microspheres with (d-ASP)6 oligomers grafted on the surface via carboxylated Poly(vinyl alcohol) (PVA)
Summary
Osteomyelitis (OM) is a dreaded complication that can affect up to 27% of patients with bone fractures [1]. For approximately 30% of patients that undergo such extensive therapies, infection re-emerges within 12 months [2]. It has been recently shown that S. aureus has the ability to deform and penetrate (sub-)micron structures in vitro [5] and this was observed microscopically in clinical bone biopsies [6]. This phenomenon is expected to contribute to the high recurrence rate of OM as bacteria residing in bone canaliculi may evade local and systemic antibiotic therapies without causing tissue necrosis and so may be missed during surgical debridement procedures
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