Lee James, Jallo George I, Penno Margaret B, Gabrielson Kathleen L, Young G David, Johnson Randolph M, Gillis Edward M, Rampersaud Charles, Carson Benjamin S, Guarnieri Michael
School of Medicine and Department of Neurosurgery, Johns Hopkins University, 817 Hunterian, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Toxicol Appl Pharmacol. 2006 Aug 15;215(1):64-70. doi: 10.1016/j.taap.2006.02.009. Epub 2006 Apr 21.
Sucrose acetate isobutyrate (SAIB) is a water insoluble, biodegradable gel used for controlled-release oral and subcutaneous drug delivery. We investigated SAIB compatibility in the rat central nervous system (CNS) by implanting solutions of SAIB in adult and in neonatal brains.
10-15 microL solutions of SAIB gels in 0-30% ethanol were injected into the cerebral cortex of adult Fischer 344 rats. Control animals were implanted with a 10 mg biodegradable poly anhydride copolymer of poly [bis (p-carboxyphenoxy) propane] anhydride and sebacic acid (PCPP:SA). Adult rats were evaluated for signs of pain and distress, including changes in posture, facial signs, and grooming behavior. 1-2 microL solutions of SAIB gels in 15% ethanol were injected into brains of 12-24 h-old rats. Neonatal rats were evaluated for survival. Adult and neonatal brains were examined by histopathology 3-48 days after implant.
Gel implants produced elliptical compression of cortical tissue, cell loss, and inflammation. Cell loss appeared to be confined to the implantation wound and associated neuronal fields. In adult rats, neurophil compression, inflammation, and cell loss appeared similar with the 10-mg PCPP:SA implants and the 10-mg SAIB implants. There was no clinical evidence of pain or distress from SAIB implants. 1-2 microL implants of SAIB-15% ethanol had no effect on survival of neonatal animals.
Brain implants of SAIB induce a mild to moderate inflammatory response and associated neuronal cell damage. The implants appeared to be biocompatible in adult and neonatal animals. These results suggest that further studies of SAIB as an injectable drug-delivery scaffold for CNS therapeutic agents are warranted.
蔗糖乙酸异丁酸酯（SAIB）是一种水不溶性、可生物降解的凝胶，用于口服和皮下控释给药。我们通过将SAIB溶液植入成年和新生大鼠脑内，研究了其在大鼠中枢神经系统（CNS）中的相容性。
将0 - 30%乙醇中SAIB凝胶的10 - 15微升溶液注入成年Fischer 344大鼠的大脑皮层。对照动物植入10毫克由聚[双（对羧基苯氧基）丙烷]酸酐和癸二酸组成的可生物降解聚酸酐共聚物（PCPP:SA）。评估成年大鼠的疼痛和痛苦迹象，包括姿势变化、面部表情和梳理行为。将15%乙醇中SAIB凝胶的1 - 2微升溶液注入12 - 24小时龄大鼠的脑内。评估新生大鼠的存活率。植入后3 - 48天通过组织病理学检查成年和新生大鼠的大脑。
凝胶植入物导致皮质组织呈椭圆形受压、细胞丢失和炎症。细胞丢失似乎局限于植入伤口及相关神经元区域。在成年大鼠中，嗜中性粒细胞受压、炎症和细胞丢失在10毫克PCPP:SA植入物和10毫克SAIB植入物中表现相似。没有临床证据表明SAIB植入物会引起疼痛或痛苦。1 - 2微升SAIB - 15%乙醇植入物对新生动物的存活率没有影响。
SAIB脑内植入物会引发轻度至中度炎症反应及相关神经元细胞损伤。这些植入物在成年和新生动物中似乎具有生物相容性。这些结果表明有必要进一步研究SAIB作为中枢神经系统治疗药物的可注射给药支架。
