The role of the fibrous capsule in the function of implanted drug-polymer sustained release systems.
Numerous studies have been carried out on drug-polymer sustained release systems designed for implantation. The majority of these efforts have been directed toward determining the in-vitro rate of drug release from specific systems or drug polymer combinations and the in-vivo studies have attempted to utilize analysis of the blood serum and excretory products as a measure of the release rate and behavior. To gain a better understanding of the influence of the local tissue environment and implant site on release behavior, we have investigated the release behavior of a gentamicin-silicone rubber system implanted in canines. Particular attention has been directed toward investigating the role that the fibrous capsule which eventually surrounds the implant plays in determining the rate and pattern of drug release. The drug burst effect was decreased by the use of a drug-free silicone rubber membrane on the gentamicin-silicone rod implant. Analysis for gentamicin in the tissue adjacent to the implant for periods up to four weeks indicated that the release rate was retarded by the development of the fibrous capsule. The temporal and spatial variations in gentamicin levels in the tissue surrounding the rod implants were determined. In addition, the influence of implant coating and gentamicin loading level in the implant on local tissue concentrations with time were also investigated. These studies provide evidence that the fibrous capsule surrounding a drug-polymer sustained release implant may influence the release behavior of the drug in an advantageous or disadvantageous manner depending upon the desired function of the sustained release system.
D000818:Animals; D002214:Capsules; D004285:Dogs; D004343:Drug Implants; D005839:Gentamicins / Q000378:metabolism; D006097:Granulation Tissue / Q000166:cytology; D007249:Inflammation / Q000209:etiology; D009132:Muscles / Q000378:metabolism; D012826:Silicone Elastomers / Q000009:adverse effects
D002214:Capsules; D004343:Drug Implants; D005839:Gentamicins; D012826:Silicone Elastomers