Efficacy of antibiotics-loaded interpenetrating network (IPNs) hydrogel based on poly(acrylic acid) and gelatin for treatment of experimental osteomyelitis: in vivo study

The safety and efficacy of gentamycin sulphate (GS)- or vancomycin hydrochloride (VCl)-loaded polymer device based on poly(acrylic acid) and gelatin crosslinked selectively using 0.3 mol % N,N'-methylene bisacrylamide and 1 wt% glutaraldehyde were evaluated by varying the drug concentration onto the devices. The placebo and drug-loaded device of AxGx (acrylic acid:gelatin: 1:1 w/w) were employed for the treatment of experimental osteomyelitis in rabbit. Rabbits were categorized into four groups. Twelve rabbits in each group were treated with 12+/-1 mg of AxGx-1a (22% w/w GS), 12+/-1 mg of AxGx-1b (44% ww GS) 16+/-1 mg of AxGx-1b (44% w/w GS) and 16+/-1 mg of AxGx-1c (44% w/w VCI). The drug concentration was measured following implantation in the adjacent tissue of femoral cavity, and serum. In femoral cavity maximum drug concentration was found on the 7th day with all the four types of devices. No drug was found after 21 days, at the local site with devices AxGx-1a and AxGx-1b (12+/-1 mg), whereas it was detected after 6 weeks with 16+/-1 mg device (44% w/w GS or VCI). Macroscopic evaluation after treatment revealed that swelling, redness, local warmth and drainage decreased depending upon the drug loading of the implants. Sequential radiographs, histology, microbiologic assay and scanning electron micrography demonstrated devices AxGx-1b and AxGx-1c (16+/-1 mg of 44% w/w drug loading) to be the most suitable device, which heals the infection after 6 weeks of treatment. No significant difference (p>0.05) in the rate of healing was observed between GS- and VCI-loaded devices. None of the implant showed toxic level of drug in serum at any given time. (C) 2004 Elsevier Ltd. All rights reserved.