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in Vivo Evaluation of Gentamicin Impregnated Polylactic Acid Beads Implanted in Sheep

Department of Veterinary Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.wdernell{at}vth.colostate.edu

S. J. Withrow

C. A. Kuntz

R. Dewell

F. B. Garry

The Departments of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523

B. E. Powers

Department of Pathology, Colorado State University, Fort Collins, CO 80523

J. E. Shively

J. D. Meyer

M. C. Manning

Department of Pharmaceutical Science, School of Pharmacy, University of Colorado Health Sciences, Center Denver, CO

R. F. Falk

T. W. Randolph

Department of Chemical Engineering, University of Colorado, Boulder, CO

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.

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