Hot melt poly-ε-caprolactone/poloxamine implantable matrices for sustained delivery of ciprofloxacin
2012
Puga, Ana M. | Rey-Rico, Ana | Magariños, Beatriz | Alvarez-Lorenzo, Carmen | Concheiro, Angel
It has been suggested that prevention and treatment of osteomyelitis could be achieved through local drug delivery using implantable devices, which provide therapeutic levels at the infection site with minimum side-effects. Physical blends of polycaprolactone (PCL) and poloxamine (Tetronic®) were prepared by applying a solvent-free hot melting approach to obtain cytocompatible implants with a tunable bioerosion rate, ciprofloxacin release profile and osteoconductive features. Differential scanning calorimetry and X-ray analysis indicate that the hydrophilic poloxamine varieties T908, T1107, and T1307 are miscible with PCL, while the hydrophobic block copolymer T1301 is immiscible. Incorporation of the block copolymer at weight ratios ranging from 25 to 75wt.% led to matrices with viscoelastic parameters in the range of those of fresh cortical bone. Once immersed in buffer the matrices underwent a similar weight loss in the first week to the content of poloxamine, followed by a slower erosion rate due to PCL. The initial rapid erosion and the increase in porosity partially explain the observed burst of ciprofloxacin release, which is more intense in the PCL:T1301 formulation due to drug/T1301 repulsion due to polarity. The matrices sustained ciprofloxacin release for several months (<50% released after 3months) and showed in vitro efficacy against Staphylococcus aureus, eradicating the bacteria in less than 48h. PCL:poloxamine was cytocompatible with osteoblasts and the matrices prepared with low proportions of T908 were also compatible with mesenchymal stem cell differentiation to osteoblasts. The influence of the nature and proportion of temperature-responsive poloxamine on the performance of PCL implantable systems was determined.
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