Ishihara Masayuki, Obara Kiyohaya, Nakamura Singo, Fujita Masanori, Masuoka Kazunori, Kanatani Yasuhiro, Takase Bonpei, Hattori Hidemi, Morimoto Yuji, Ishihara Miya, Maehara Tadaaki, Kikuchi Makoto
Research Institute, National Defense Medical College, 3-2 Namiki, Tokorozawa, 359-8513, Japan.
J Artif Organs. 2006;9(1):8-16. doi: 10.1007/s10047-005-0313-0.
An aqueous solution of photocrosslinkable chitosan containing azide groups and lactose moieties (Az-CH-LA) incorporating paclitaxel formed an insoluble hydrogel within 30 s of ultraviolet light (UV) irradiation. The chitosan hydrogel showed strong potential for use as a new tissue adhesive in surgical applications and wound dressing. The fibroblast growth factor (FGF)-2 molecules retained in the chitosan hydrogel and in an injectable chitosan/IO(4)-heparin hydrogel remain biologically active, and were gradually released from the hydrogels as they biodegraded in vivo. The controlled release of biologically active FGF-2 molecules from the hydrogels caused induction of angiogenesis and collateral circulation occurred in healing-impaired diabetic (db/db) mice and in the ischemic limbs of rats. Paclitaxel, which is an antitumor reagent, was also retained in the chitosan hydrogel and remained biologically active as it was released on degradation of the hydrogel in vivo. The chitosan hydrogels incorporating paclitaxel effectively inhibited tumor growth and angiogenesis in mice. The purpose of this review is to describe the effectiveness of chitosan hydrogel as a local drug delivery carrier for agents (e.g., FGF-2 and paclitaxel) to control angiogenesis. It is thus proposed that chitosan hydrogel may be a promising new local carrier for drugs such as FGF-2 and paclitaxel to control vascularization.
含有叠氮基团和乳糖部分(Az-CH-LA)并结合了紫杉醇的可光交联壳聚糖水溶液在紫外线(UV)照射30秒内形成了不溶性水凝胶。壳聚糖水凝胶在外科手术应用和伤口敷料中作为一种新型组织粘合剂具有很大的应用潜力。保留在壳聚糖水凝胶和可注射壳聚糖/IO(4)-肝素水凝胶中的成纤维细胞生长因子(FGF)-2分子保持生物活性,并随着水凝胶在体内降解而逐渐从水凝胶中释放出来。水凝胶中生物活性FGF-2分子的控释导致愈合受损的糖尿病(db/db)小鼠和大鼠缺血肢体中血管生成和侧支循环的诱导。作为抗肿瘤试剂的紫杉醇也保留在壳聚糖水凝胶中,并在水凝胶在体内降解时释放出来时保持生物活性。含有紫杉醇的壳聚糖水凝胶有效抑制了小鼠肿瘤生长和血管生成。本综述的目的是描述壳聚糖水凝胶作为局部药物递送载体对控制血管生成的药物(如FGF-2和紫杉醇)的有效性。因此,有人提出壳聚糖水凝胶可能是一种有前途的新型局部载体,用于递送FGF-2和紫杉醇等药物以控制血管形成。