Characterization of biodegradable chitosan microspheres containing vancomycin and treatment of experimental osteomyelitis caused by methicillin-resistant Staphylococcus aureus with prepared microspheres.
The 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 microm. 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 microspheres 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.
Cevher
Erdal
E
Istanbul University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Istanbul, Turkey. erdalcevher@superonline.com
Orhan
Zafer
Z
Mülazimoğlu
Lütfiye
L
Sensoy
Demet
D
Alper
Murat
M
Yildiz
Ayca
A
Ozsoy
Yildiz
Y
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D001673:Biodegradation, Environmental; D048271:Chitosan / Q000737:chemistry; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004339:Drug Compounding; D004343:Drug Implants; D007273:Injections, Intramuscular; D008297:Male; D016106:Methicillin Resistance; D008863:Microspheres; D010019:Osteomyelitis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification; D014640:Vancomycin / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D004343:Drug Implants; D014640:Vancomycin; D048271:Chitosan