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Biodegradable microspherical implants containing teicoplanin for the treatment of methicillin-resistant Staphylococcus aureus osteomyelitis

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Abstract

Background

The aim of this study was to prepare poly(d,l-lactide-co-glycolide) (PLGA) microspherical implants containing teicoplanin (TCP) using a double emulsion solvent evaporation method and to evaluate its efficacy for the local treatment of chronic osteomyelitis.

Methods

The particle size and distribution, morphological characteristics, thermal behaviour, drug content, encapsulation efficiency and in vitro release assessments of the formulations were carried out. Sterile TCP–PLGA microspheres were implanted in the proximal tibia of rats with methicillin resistant Staphylococcus aureus (MRSA) osteomyelitis. After 3 weeks of treatment, bone samples were analysed with a microbiological assay and evaluated histopathologically.

Results

Microspheres between the size ranges of 2.01 and 3.91 μm were obtained. Production yield of all formulations was found to be higher than 82% and encapsulation efficiencies of 33.6–69.8% were obtained. DSC thermogram showed that the TCP was in an amorphous state in microspheres. In vitro drug release studies had indicated that the drug release rate of microspheres was decreased upon increasing the polymer:drug ratio. Based on the in vivo data, rats treated with implants and intramuscular injection showed 1.7 × 103 ± 1.3 × 103 and 5.8 × 104 ± 5.3 × 104 colony forming unit of MRSA in 1 g bone samples (CFU/g), respectively (P < 0.01).

Conclusions

The in vitro and in vivo studies had shown that the TCP–PLGA microspheres were effective for the treatment of chronic osteomyelitis in an animal experimental model. Hence, these microspheres may be potentially useful in the clinical setting with the need for further investigation for optimal dosing of TCP–PLGA microspheres.

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Conflict of interest statement

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Authors and Affiliations

  1. Department of Orthopaedics, School of Medicine, Düzce University, 81620, Düzce, Turkey

    Zafer Orhan

  2. Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey

    Erdal Cevher, Ayca Yıldız & Demet Sensoy

  3. Department of Pathology, School of Medicine, Marmara University, Istanbul, Turkey

    Rengin Ahıskalı

  4. Department of Infectious Diseases and Clinical Microbiology, School of Medicine, Marmara University, Istanbul, Turkey

    Lütfiye Mülazımoğlu

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  1. Zafer Orhan
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  2. Erdal Cevher
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  6. Lütfiye Mülazımoğlu
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Correspondence to Zafer Orhan.

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Orhan, Z., Cevher, E., Yıldız, A. et al. Biodegradable microspherical implants containing teicoplanin for the treatment of methicillin-resistant Staphylococcus aureus osteomyelitis. Arch Orthop Trauma Surg 130, 135–142 (2010). https://doi.org/10.1007/s00402-009-0886-9

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