Azab Abdel Kareem, Doviner Victoria, Orkin Boris, Kleinstern Jackie, Srebnik Morris, Nissan Aviram, Rubinstein Abraham
Department of Pharmaceutics, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel.
J Biomed Mater Res A. 2007 Nov;83(2):414-22. doi: 10.1002/jbm.a.31256.
The aim of the present study was to evaluate the toxicity of biodegradable hydrogels in the rat with a future aim of utilizing this hydrogel as a vehicle for brachytherapy delivery in cancer patients. Two types of chitosan hydrogels: fast degrading and slow degrading; were prepared and surgically implanted in rats. The adjacent tissue response to the gels after subcutaneous and intraperitoneal implantation was examined histologically and found to be identical to typical foreign body response and was milder than the response to absorbable surgical sutures (Vicril). Neither tissue damage nor gel fragments could be detected in distant organs (brain, heart, lungs, liver, spleen, kidney, and sternal bone marrow) after implantation of the hydrogels. The degradation mechanism of the gels was studied in vivo, and it was deduced that an oxidative process degraded the chitosan. Loading the hydrogels with a radioisotope (131I-norcholesterol) caused a severe tissue response and necrosis in adjacent tissues only at a distance of several microns. It is concluded that crosslinked chitosan implants could serve as alternative, biocompatible, and safe biodegradable devices for radioisotope delivery in brachytherapy for cancer.
本研究的目的是评估可生物降解水凝胶对大鼠的毒性,未来旨在将这种水凝胶用作癌症患者近距离放射治疗的载体。制备了两种类型的壳聚糖水凝胶:快速降解型和缓慢降解型,并通过手术植入大鼠体内。对皮下和腹腔内植入水凝胶后相邻组织的反应进行了组织学检查,发现其与典型的异物反应相同,且比可吸收手术缝线(维克瑞)引起的反应更轻微。水凝胶植入后,在远处器官(脑、心脏、肺、肝、脾、肾和胸骨骨髓)中未检测到组织损伤或凝胶碎片。对水凝胶在体内的降解机制进行了研究,推断壳聚糖是通过氧化过程降解的。仅在几微米的距离内,向水凝胶中加载放射性同位素(131I-降胆固醇)会在相邻组织中引起严重的组织反应和坏死。得出的结论是,交联壳聚糖植入物可作为癌症近距离放射治疗中放射性同位素递送的替代、生物相容性和安全的可生物降解装置。