The role of the fibrous capsule in the function of implanted drug‐polymer sustained release systems

Abstract

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.

In vivo biocompatibility studies of poly(D,L-lactide)/poly(ethylene glycol)-poly(L-lactide) microspheres containing all-trans-retinoic acid

“…The extensively deposited collagen at the implantation sites might act as a permeability barrier and restrict the diffusion of drugs [26]. Moreover, a thick band of broblasts, which are known to actively metabolize RA [27], was formed at the boundary of the brous tissue layer and the exudates from the 30th to the 45th day.…”

The Role of Polymer Permeability in the Control of Drug Release

“…85 More recent additions to such a list include studies on nicotine,86 antiarrhythmic agents,87 prostaglandins 88 and gentamicin. 89 The latter reference is of interest because of its particular attention to the effects of fibrous capsule formation around an implanted reservoir device. Such tissue reaction is often regarded as a major problem in the use of implanted controlled release devices because the diffusional resistance offered by a fibrous envelope may have serious effects on the release profile of a drug.…”

Host Response to Long Acting Injections and Implants

“…This condensation or compaction leads to an increase in density of the collagen fi bers. This classic end-stage fi brous capsule formation with the normal foreign body reaction at the implant interface is seen with polymers such as polyethylene, poly(ethylene-vinyl acetate), and other nondegradable polymers [ 8,64 ] .…”

“…This classic foreign body reaction, indicating biocompatibility, is surrounded by a thin fi brous capsule that is composed predominantly of collagen with a few fi broblasts present within the capsule. End-stage fi brous capsule formation does not usually contain the vascular capillaries that are easily recognized in the developing granulation tissue, which leads to fi brous capsule formation [ 64 ] . In general, in end-stage fi brous capsule formation, the vascular capillaries disappear and the fi brous capsule may be seen to shrink in regard to its thickness.…”