In vitro and in vivo release of gentamicin from biodegradable discs.
Osteomyelitis is an infection of the bone and successful treatment involves the removal of the affected bone and the tissue by a surgical procedure following prolonged systemic and local antibiotic therapy for 4 to 6 weeks. The current local treatment is done by poly methyl methacrylate (PMMA) beads loaded with gentamicin and PMMA, being nondegradable, is to be removed by a second surgical procedure. The current study aims to develop a biodegradable composition that gives sustained release and hence reducing the need for a second surgery. Gentamicin-loaded discs were produced by compressing microparticle-gentamicin mixture obtained by spray drying a mixture of gentamicin in a solution of a biodegradable polymer. Different copolymers of poly (DL-lactic-co-glycolic acid) (PLGA) were used to study the effect of copolymer ratio and the hydrophilic-hydrophobic nature of the polymer. Theoretical drug loading up to 25% were studied and it was observed that 10% drug loading was optimum for gentamicin to be used as solid in spray drying. The results showed that about 60% of the drug is released in about 5 to 6 days and the remaining drug is released in about 30 days in total. An in vivo study was carried on rabbit femur and the local area and systemic concentration of gentamicin was monitored. It was observed that the local area concentration of gentamicin was above minimum inhibitory concentration for more than 20 days and this was also validated by computer simulations.
Naraharisetti
Pavan Kumar
PK
Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117576, Singapore.
Guan Lee
Herman Chian
HC
Fu
Yin-Chih
YC
Lee
Duu-Jong
DJ
Wang
Chi-Hwa
CH
D000818:Animals; D001673:Biodegradation, Environmental; D003692:Delayed-Action Preparations / Q000737:chemistry*; D005269:Femur; D005839:Gentamicins / Q000008:administration & dosage*; D007700:Kinetics; D019344:Lactic Acid / Q000627:therapeutic use; D010019:Osteomyelitis / Q000188:drug therapy; D011100:Polyglycolic Acid / Q000627:therapeutic use; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000627:therapeutic use; D011817:Rabbits
D003692:Delayed-Action Preparations; D005839:Gentamicins; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid