Tamargo R J, Epstein J I, Reinhard C S, Chasin M, Brem H
Department of Neurological Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
J Biomed Mater Res. 1989 Feb;23(2):253-66. doi: 10.1002/jbm.820230209.
We report the biocompatibility in the rat brain of a controlled-release, biodegradable polymer, the polyanhydride poly-[bis(p-carboxyphenoxy)propane-sebacic acid] copolymer (PCPP-SA) in a 20:80 formulation. The biodegradable polyanhydride can be used for drug delivery directly into the brain, circumventing the difficulties posed by the blood-brain barrier and avoiding the consequences of having to administer toxic doses systematically to reach therapeutic doses in the central nervous system. The tissue reaction in the presence of PCPP-SA was compared to that seen with other standard neurosurgical implants. Fifty-six adult Sprague-Dawley rats were assigned to one of seven groups and underwent bilateral frontal lobe implantation of PCPP-SA (42 hemispheres), Surgicel (oxidized regenerated cellulose) (35 hemispheres), or Gelfoam (absorbable gelatin sponge) (35 hemispheres). None of the animals showed any behavioral changes or neurological deficits suggestive of either systemic or localized toxicity from the biodegradable polyanhydride, all surviving to the scheduled data of sacrifice. PCPP-SA evoked a well localized inflammatory reaction, comparable to that of Surgicel, which resolved as the PCPP-SA polymer degraded over five weeks. The biodegradable polyanhydride has been shown in this study to be nontoxic and biocompatible in the rat brain, when compared to standard neurosurgical implants.
我们报告了一种控释、可生物降解聚合物——20:80配方的聚酸酐聚[双（对羧基苯氧基）丙烷-癸二酸]共聚物（PCPP-SA）在大鼠脑内的生物相容性。这种可生物降解的聚酸酐可用于将药物直接递送至脑内，规避血脑屏障带来的困难，并避免为在中枢神经系统中达到治疗剂量而不得不系统性给予有毒剂量药物所产生的后果。将存在PCPP-SA时的组织反应与其他标准神经外科植入物所引发的反应进行了比较。56只成年Sprague-Dawley大鼠被分为七组之一，接受了PCPP-SA（42个半球）、外科用氧化纤维素（Surgicel，35个半球）或明胶海绵（Gelfoam，35个半球）的双侧额叶植入。没有动物表现出任何行为变化或神经功能缺损，提示可生物降解聚酸酐存在全身或局部毒性，所有动物均存活至预定的处死日期。PCPP-SA引发了局部炎症反应，与外科用氧化纤维素相当，随着PCPP-SA聚合物在五周内降解，炎症反应消退。与标准神经外科植入物相比，本研究表明这种可生物降解聚酸酐在大鼠脑内无毒且具有生物相容性。
