Simulation of gentamicin delivery for the local treatment of osteomyelitis.
In order to understand the effect of antibiotics delivery to bone tissue, by biodegradable polymeric drug disc, for the treatment of osteomyelitis, a three-dimensional simulation model is developed. The simulation investigates the effect of pressure-induced convection on drug distribution, by taking into account the pressure gradient that exists between capillaries and interstitial space, and also as a result of the surgical opening. The clotting process at the surgical opening is incorporated into the simulation, and the effect of clotting duration is investigated. The clotting duration for the baseline simulation is 2 days and it is observed that increasing this duration depresses the mean drug concentration in the marrow and cortical bone. The effect of double burst release profile is also studied and it is observed that drug concentration drops too rapidly after the first burst to provide any therapeutic effect. However, it is shown that the drug concentration after the second burst stays above the minimum inhibitory concentration of the bacteria for a longer period of time, than would have been observed for a mono-burst release. Inserting non-biodegradable polymethylmethacrylate (PMMA) beads into bone seems to cause a higher average concentration of drug in the marrow. However, this could be brought about by the difference in the geometry between the disc and the bead, and the amount of drug packed in each bead. Further simulations on the management of dead space shows the ineffectiveness of having the void filled up with surgical gel as it becomes an additional barrier to drug delivery to the infected tissues.
Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117576.
Chian Guan
CG
Lee
Yin-Chih
YC
Fu
Chi-Hwa
CH
Wang
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001672:Biocompatible Materials; D001673:Biodegradation, Environmental; D003198:Computer Simulation; D016503:Drug Delivery Systems; D005839:Gentamicins / Q000008:administration & dosage*; D008863:Microspheres; D010019:Osteomyelitis / Q000188:drug therapy*; D019904:Polymethyl Methacrylate; D011817:Rabbits; D013997:Time Factors
D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D005839:Gentamicins; D019904:Polymethyl Methacrylate