In vivo Evaluation of Gentamicin Impregnated Polylactic Acid Beads Implanted in Sheep

Abstract

The biocompatibility and levels of gentamicin released from a poly(lactic acid) (PLA) polymer system in the serum, milk and tissue of a food animal model were determined. Microsphere particles of PLA containing 6.7% (w/w) gentamicin were compressed into 5 mm beads onto suture. Three groups of three cull ewes each were implanted with a bead string of PLA/gentamicin in one caudal thigh (muscle) and PLA control beads in the opposite thigh for 2, 4 and 6 months. Milk and serum samples were obtained at regular intervals until sacrifice. Following sacrifice, implant sites, kidney, liver and skeletal muscle were sampled for gentamicin concentration and histologic evaluation. Serum gentamicin peaked by day 1 (up to 0.7 μg/mL) and decreased to near zero by day 16 in all groups. Milk levels were measurable (>0.01 μg/mL) only on 2 days, in one sheep. Kidney gentamicin levels approached 2 ppm, and liver gentamicin levels approached 1 ppm in the 6-month group. A mild to moderate foreign body reaction was seen histologically in all PLA/gentamicin and PLA control implantation sites. Gentamicin released from this implanted polymer system produced low serum and milk concentrations, but developed renal accumulation beyond tolerated levels (30 ppb). Polymer/antibiotic delivery systems show promise for the treatment of local infections in veterinary patients.

The Chemistry and Applications of Antimicrobial Polymers: A State-of-the-Art Review

“…Gentamicine-release testing revealed residual antibiotic release after being 5 years in situ. Gentamicin implants were impregnated in sheep and showed that the system is promising for the treatment of local infections in veterinary patients …”

Study of the Influence of Bone Cement Type and Mixing Method on the Bioactivity and the Elution Kinetics of Ciprofloxacin

“…Antibiotic-loaded acrylic bone cement, described by Buchholz and Engelbrecht [1], is a well-established tool in the prophylaxis [2,3] and treatment of orthopedic infections [4] in humans and animals [5], with meta-analyses indicating that its use reduces the infection rate [6]. Polymethylmetacrylate -PMMA -is characterized by excellent biocompatibility with low intrinsic toxicity and inflammatory activation [7], but experience has shown that not all antibiotics have the properties necessary for their incorporation in this cement.…”

A novel gentamicin-releasing wound dressing prepared from freshwater fish Cyprinus carpio collagen cross-linked with carbodiimide

“…Several antibiotic-releasing collagen sponges or beads produced from various materials intended for local treatment use are currently being investigated or are already commercially available. 5,6,16 Gentamicin makes up the most frequently studied and clinically applied antibiotic with respect to collagen-based drug delivery systems and, moreover, it has already been approved for clinical use. Gentamicin is suitable for post-operative wound treatment applications since it is highly active against G– and, in high concentrations, against G+ bacteria.…”