Anderson J M, Niven H, Pelagalli J, Olanoff L S, Jones R D
J Biomed Mater Res. 1981 Nov;15(6):889-902. doi: 10.1002/jbm.820150613.
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.
针对设计用于植入的药物-聚合物缓释系统，已经开展了大量研究。这些研究大多致力于确定特定系统或药物-聚合物组合的体外药物释放速率，而体内研究则试图利用血清和排泄产物分析来衡量释放速率和行为。为了更好地理解局部组织环境和植入部位对释放行为的影响，我们研究了植入犬体内的庆大霉素-硅橡胶系统的释放行为。特别关注的是研究最终包裹植入物的纤维囊在决定药物释放速率和模式中所起的作用。在庆大霉素-硅橡胶棒状植入物上使用无药硅橡胶膜可降低药物突释效应。对植入物周围组织长达四周的庆大霉素分析表明，纤维囊的形成会延迟释放速率。测定了棒状植入物周围组织中庆大霉素水平的时空变化。此外，还研究了植入物涂层和植入物中庆大霉素负载水平随时间对局部组织浓度的影响。这些研究提供了证据，表明围绕药物-聚合物缓释植入物的纤维囊可能根据缓释系统的预期功能，以有利或不利的方式影响药物的释放行为。
