It was not possible to preserve the function of the radiocarpal joint and so this technique cannot be recommended currently. Further study is needed to evaluate whether or not IORT can be considered in combination with pancarpal plating and possibly curettage and cementation of the tumor to prevent subchondral bone collapse.

Cisplatin was incorporated into an in-situ forming biodegradable implant delivery system (ATRIGELO) consisting of a biodegradable polymer dissolved in a pharmaceutically acceptable solvent. The polymer solution with the suspended cisplatin was injected subcutaneously into the flank or shoulder of six healthy beagle dogs where the water-insoluble polymer precipitated upon contact with body fluids and formed a solid implant for the controlled release of the drug. Each dog received four injections, spaced thirty days apart, of a formulation containing either poly(DL-lactide-co-caprolactone) (PLC) or pely(DL-lactide-co-glycolide) (PLGA) dissolved in dimethyl sulfoxide (DM8O) and loaded with 8% by weight cisplatin. Dosage levels of 70, 105, and 157.5 mg/m2 were used to determine dosage escalation effects. Injections of the same formulations without the drug served as controls. Samples of blood were taken at appropriate times over the four months of treatment and analyzed for platinum concentration by atomic absorption spectroscopy. Local tissue and systemic toxicities were also determined. Both formulations exhibited sustained release of cisplatin with peak serum concentrations of platinum being attained in about two days followed by gradually decreasing platinum levels to day thirty. Consistent drug release profiles were observed for each of the four thirty-day treatment periods. The dosage escalation results exhibited an approximate 50% increase in peak platinum levels and area-under-the-curve (AUC) values for each 50% increase in drug dose. Local tissue toxicity to the cisplatin-containing implants was variable and appeared to be unrelated to dose level or direction number. Tissue reaction to the implants without drug was minimal indicating a role of cisplatin in the tissue reactions. Systemic toxicity, as judged by clinical parameters and clinicopathologic evaluation, was not noted at any dose level or injection time.

A new method for preparing poly(L-lactide) (PLA) biodegradable beads impregnated with an ionic aminoglycoside, gentamycin, is described. The process employs hydrophobic ion pairing to solubilize gentamycin in a solvent compatible with PLA, followed by precipitation with a compressed antisolvent (supercritical carbon dioxide). The resulting precipitate is a homogeneous dispersion of the ion-paired drug in PLA microspheres. The microspheres are approximately 1 microm in diameter and can be compressed into beads (3-6 mm in diameter) strung on surgical sutures for implantation. The bead strings exhibit no significant change in release kinetics upon sterilization with a hydrogen peroxide plasma (Ster-Rad). The kinetics of gentamycin release from the PLA beads are consistent with a matrix-controlled diffusion mechanism. While nonbiodegradable poly(methyl methacrylate) (PMMA) beads initially release gentamycin in a similar manner, the drug release from PMMA ceases after 8 or 9 weeks, while the PLA beads continue to release drug for over 4 months. Moreover, only 10% of the gentamycin is released from the PMMA beads, while PLA beads release more than 60% of their load, if serum is present in the release medium. The PLA system displays improved release kinetics relative to PMMA, is biodegradable, is unaltered by gas sterilization, can be used for a range of antibiotics, and can be manipulated without disintegration. These are all desirable properties for an implantable drug delivery system for the prevention or treatment of osteomyelitis.

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.

No abstract