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Öğe Characterization of biodegradable chitosan microspheres containing vancomycin and treatment of experimental osteomyelitis caused by methicillin-resistant staphylococcus aureus with prepared microspheres(Elsevier Science Bv, 2006) Cevher, Erdal; Orhan, Zafer; Mulazimoğlu, Lütfiye; Şensoy, Demet; Alper, Murat; Yıldız, Ayça; Özsoy, YıldızThe biodegradable chitosan microspheres containing vancomycin hydrochloride (VANCO) were prepared by spray drying method with different polymer:drug ratios ( 1: 1, 2:1, 3:1 and 4: 1). Thermal behaviour, particle size and distribution, morphological characteristics, drug content, encapsulation efficiency, in vitro release assessments of formulations have been carried out to obtain suitable formulation which shows sustained-release effect when implanted. Sterilized VANCO loaded microspheres were implanted to proximal tibia of rats with methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. Intramuscular (IM) injection of VANCO for 21 days was applied to another group for comparison. After 3 weeks of treatment, bone samples were analysed with a microbiological assay. According to the results, encapsulation efficiency and yield of microspheres in all formulations were higher than 98% and 47%, respectively. Particle sizes of microspheres were smaller than 6 mu m. All microsphere formulations have shown sustained-release effect. In vitro drug release rate decreased due to the increase in polymer:drug ratio but no significant difference was seen between these results (p > 0.05). Based on our in vivo data, rats implanted VANCO-loaded chitosan inicrospheres and administered IM injection showed 3354 3366 and 52500 25635 colony forming, unit of MRSA in 1g bone samples (CFU/g), respectively. As a result, implanted VANCO-loaded microspheres were found to be more effective than IM route for the treatment of experimental osteomyelitis.Öğe Preparation and In vivo evaluation of gelatine implants containing EGF-PLGA microspheres in tendon healing(University of Istanbul, 2007) Orhan, Zafer; Cevher, Erdal; Gül, Mine Orlu; Alper, Murat; Özçelik, Derya; A?artan, Canan; Öner, FilizEpidermal Growth Factor (EGF) has been shown to improve tissue healing according to several well-design experimental studies. The possible role of EGF in tendon healing has not been defined. However, the main drawback of studies on the efficiency of EGF is to provide a long-term constant supply of EGF to target cells. In this respect, we hypothesized that the microspheres contained EGF would overcome this problem by providing a constant local supply of EGF. This study had investigated the role of EGF-loaded microspheres in a rat model for tendon heali*ng. EGF-loaded particles were prepared by double emulsion solvent evaporation method and embedded into gelatine implant. Implants containing microspheres which are equivalent to 10?g EGF (I-MS EGF10) and 2?g EGF (I-MSEGF2) were applied to Wistar albino rats. Histological and biomechanical studies were performed on to 21 days treated rats. I-MSEGF10 group showed prominent fibrosis and increased neoangiogenesis. Although, there was no major difference between I-MSEGF10 group and negative control group for the fibroblast and collagen proliferation (p>0.05), the difference for inflammation was statistically significant between same groups (p<0.05). Consequently, the approach of combining EGF and microspheres to extend the EGF release and in the same time increasing the contact time of EGF to tendon tissue was achievable. However, according to the obtained histological and biomechanical results, gelatine implants including EGF loaded microspheres were not found effective in tendon healing.Öğe The preparation of ciprofloxacin hydrochloride-loaded chitosan and pectin microspheres - their evaluation in an animal osteomyelitis model(British Editorial Soc Bone Joint Surgery, 2006) Orhan, Zafer; Cevher, Erdal; Mülazımoğlu, Lütfiye; Gürcan, Duygu; Alper, Murat; Araman, Ahmet; Özsoy, YıldızCiprofloxacin hydrochloride-loaded microspheres were prepared by a spray-drying method using pectin and chitosan. The effects of different polymers and drug ratios were investigated. The most appropriate carriers were selected by in vitro testing. A rat methicillin-resistant Staphylococcus aureus osteomyelitis model was used to evaluate the effects of the loaded microspheres. The drug was released rapidly from the pectin carrier but this was more sustained in the chitosan formulation. Chitosan microspheres loaded with ciprofloxacin hydrochloride were more effective for the treatment of osteomyelitis than equivalent intramuscular antibiotics.Öğe Sodium fusidate-poly(D,L-lactide-co-glycolide) microspheres: Preparation, characterisation and in vivo evaluation of their effectiveness in the treatment of chronic osteomyelitis(Taylor & Francis Ltd, 2007) Cevher, Erdal; Orhan, Zafer; Şensoy, Demet; Ahıskalı, Rengin; Kan, Pei LeePurpose: The aim of this study was to prepare poly(D, L- lactide-co-glycolide) (PLGA) microspheres containing sodium fusidate ( SF) using a double emulsion solvent evaporation method with varying polymer: drug ratios (1: 1, 2.5: 1, 5: 1) and to evaluate its efficiency 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 had been carried out. Sterilized SF-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. Results: PLGA microspheres between the size ranges of 2.16-4.12 mu m were obtained. Production yield of all formulations was found to be higher than 79% and encapsulation efficiencies of 19.8-34.3% were obtained. DSC thermogram showed that the SF was in an amorphous state in the microspheres and the glass transition temperature ( Tg) of PLGA was not influenced by the preparation procedure. In vitro drug release studies had indicated that these microspheres had significant burst release and their drug release rates were decreased upon increasing the polymer: drug ratio (p < 0.05). Based on the in vivo data, rats implanted with SF-PLGA microspheres and empty microspheres showed 1987 +/- 1196 and 55526 +/- 49086 colony forming unit of MRSA in 1 g bone samples (CFU/g), respectively (p < 0.01).
