Biodegradable Controlled Antibiotic Release Devices for Osteomyelitis: Optimization of Release Properties

Abstract

Controlled antibiotic release films, melt-extruded cylinders, and suspension-extruded/coated cylinders were manufactured from biodegradable poly(D,L-lactide) (PDLLA) and poly(D,L-lactide-co-epsilon-caprolactone). These devices have potential application in the treatment of osteomyelitis. The in-vitro release properties of the devices were examined with drug loadings varying from 16 to 50%. Gentamicin sulphate films and melt-extruded gentamicin/PDLLA cylinders demonstrated a large initial burst and incomplete release. The films and melt-extruded cylinders made from poly(D,L-lactide-co-epsilon-caprolactone), low mol. wt poly(D,L-lactide), and a mixture of D,L-lactic acid oligomer and high mol. wt poly(D,L-lactide), did not remain intact during the entire release period. While this is undesirable, these materials do have the advantage of not requiring a processing temperature of greater than 110 degrees C. Antibiotic release from high mol. wt PDLLA-coated gentamicin/PDLLA cylinders, with 40 and 50% loading, was very rapid. The antibiotic could only diffuse out through the open ends of the cylinder. Coated gentamicin sulphate cylinders with 20 and 30% drug loading gave the most promising properties in terms of a small initial burst, and a gradual and sustained release. The release rate and duration from the coated cylinders could be adjusted by cutting the cylinder into different lengths; the time required for 90% of the entrapped gentamicin to be released into water from 30% loaded PDLLA-coated cylinders 0.2, 0.4, 0.7 and 1 cm in length was 1000, 1700, 2300, and 2800 h, respectively. This offers a convenient method to adjust the release to meet the specific antibiotic requirement of different patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Potential of bone scaffolds containing vancomycin and bone morphogenetic protein-2 in a rat model of osteomyelitis

“…Surgery is used to remove diseased bone and tissue or to drain pus, which often leaves an empty space in the bone. Placement of polymethylmethacrylate (PMMA) beads containing gentamicin at the defect following a thorough debridement has been recommended [13]. However, the stepwise procedures have proven to be inadequate, because of the need for secondary surgery to remove the beads before implantation of a bone graft.…”

“…The animals were sacrificed 8 weeks after implantation. Tissues from sites of osteomyelitis were excised for bacterial culture [12,13]. All of the right tibias were extracted for X-ray examination, and then fixed in 10% v/v formaldehyde in PBS for 24 h, decalcified in 3 mole L −1 HCl, and imbedded in paraffin wax.…”

Bioactivity of gentamicin contained in novel transdermal drug delivery systems (TDDS) formulated with biodegradable polyesters

“…The patches were characterized according to standard procedures with respect to physical appearance, thickness (Devi et al, 2003), weight variation (Gupta and Mukherjee, 2003), moisture content (Chang et al, 2006), moisture uptake (Lyman, 2007), film folding endurance (Zhang et al, 1994), drug content (Chang et al, 2006;Bazigha et al, 2011), in vitro bioadhesive strength (Ganesh et al, 2011;Verma and Chandak, 2009) and skin irritancy (National Committe for Clinical Laboratory Standards, 2003).…”

The use of antibiotic-impregnated fibrin sealant for the prevention of surgical site infection associated with spinal instrumentation

“…Fibrin glue, as well as other biodegradable materials, including highmolecular-weight biodegradable poly(D, L-lactide) cylinders, calcium hydroxyapatite beads, and polyglycolide beads, have been studied as potential local antibiotic delivery systems with successful results [4][5][6][7]. Fibrin can exist as a polymer in the body for some time, and it is thereafter absorbed by fibrinolysis.…”