Characteristics of chitosan antitumor sustained-release drugs

doi:10.3969/j.issn.2095-4344.2013.08.026

Abstract

Abstract:

BACKGROUND: Tumor is serious harmful to human health, and the application of effective chemical drug therapy has great significance.
OBJECTIVE: To analyze the mechanism and the therapeutic effect of drug-loaded chitosan sustained-release system on the treatment of tumor.
METHODS: The mechanism and the therapeutic effect of drug-loaded chitosan sustained-release system on the treatment of tumor was analyzed, as well as the characteristics and anti-tumor effect of chitosan and various chitosan-loaded anti-tumor drugs, such as doxorubicin, epirubicin, epirubicin, 5-fluorouracil and paclitaxel.
RESULTS AND CONCLUSION: Chitosan anti-tumor-sustained release drug materials have good drug release properties and anti-tumor properties, it can load variety of commonly used antitumor drugs, control the drug release rate, extend the drug action time, maintain the effective drug concentration and decrease the toxicity and side effects of drugs, it also has targeting effect on tumor and tissues and organs, and it can increase the therapeutic effect of chemotherapeutic drugs on tumor significantly.

Key words: biomaterials, academic discussion of biomaterials, anti-tumor, sustained release, drugs, chitosan, cells, nanometer, norcantharidin, adriamycin, pharmorubicin, epirubicin, 5-fluorouracil, paclitaxel, folic acid

CLC Number:

R318

Ling Ya-qin. Characteristics of chitosan antitumor sustained-release drugs[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(8): 1489-1496.

Figures/Tables 6

2.1 壳聚糖抗肿瘤缓释药物材料的抗肿瘤机制 2.1.1 壳聚糖抗肿瘤药物缓释材料释放药物机制壳聚糖纳米载药缓释材料的药物释放机制分为3种：①解吸释放。解吸释放就是通过吸附方式结合在纳米粒上的药物解吸附的过程，解吸释放过程与药物突释现象的产生相关。②通过纳米粒外壁的破裂释放。纳米粒外壁的破裂分为外壁降解和外壁崩解2种方式。纳米粒外壁的降解释放药物，即纳米粒表面的逐层降解导致药物释放的过程，其降解过程可分为生物降解、光降解、热降解以及氧化降解等形式。生物降解是通过形成纳米粒的聚合物主链断裂降解为小分子，或者聚合物通过水解反应、离子化反应等途径降解为水溶性化合物或高分子的过程。载体材料的降解过程可以调控药物的释放速率。外壁崩解是由于纳米粒自身稳定性差或者受到外界刺激而引起纳米粒的整体崩解，外壁崩解过程也可以引起药物突释现象。③扩散释放。即药物从纳米粒迁移至生物体的物理过程。扩散释放药物分为通过纳米粒外壳扩散渗透和通过纳米粒外壳的空洞扩散2种途径。影响壳聚糖纳米载药缓释材料的药物释放因素：①纳米粒径。粒径越大，药物缓释效果越好。②壳聚糖的分子量。分子量高的壳聚糖纳米粒缓释效果较好。原因是高分子量的壳聚糖溶解度较低，与介质溶液接触的载药纳米微粒外围形成的凝胶层粘度较高，药物释放相对缓慢。③壳聚糖浓度以及壳聚糖与药物的质量比例。一般认为，壳聚糖浓度越高，壳聚糖与药物质量比例越大，药物载运率越小，药物从壳聚糖基质中扩散进入生物介质的速率越低。 2.1.2 壳聚糖抗肿瘤缓释药物材料的抗肿瘤作用机制 ①肿瘤细胞具有比正常细胞表面更多的负电荷，而壳聚糖是带正电荷的生物大分子，因此，壳聚糖所带的正电荷对肿瘤细胞表面具有选择性吸附和电中和作用，增加肿瘤部位的药物浓度以及作用时间，从而发挥抗肿瘤的作用。②壳聚糖还可以直接抑制肿瘤细胞的增殖，并通过活化免疫系统促进机体抗肿瘤作用，从而与抗肿瘤药物发挥协同作用。③肿瘤细胞对壳聚糖纳米粒具有选择性吞噬作用，增加药物对肿瘤细胞的抑制效果，降低药物的外周毒副作用。 2.2 壳聚糖抗肿瘤缓释药物材料的抗肿瘤性能 2.2.1 壳聚糖去甲斑蝥素复合物的抗肿瘤性能去甲斑蝥素是斑蝥属昆虫南方大斑蝥和黄黑小斑蝥的虫体所含斑蝥素的合成衍生物，是治疗肝癌的药物。王红昌[8]、欧阳海燕[9]、冯炜玮[10]和王钦[11]分别对壳聚糖去甲斑蝥素复合物的抗肿瘤性能进行了研究，发现壳聚糖去甲斑蝥素复合物药物缓释系统对肝癌细胞具有较强的杀伤作用，具体分析结果见表1。 2.2.2 壳聚糖载阿霉素和表阿霉素偶合物的抗肿瘤性能阿霉素和表阿霉素都是蒽环糖甙抗生素，具有广谱抗癌活性，对各种实体瘤均有良好的治疗作用，常用于治疗乳腺癌、胃癌、肺癌、结肠癌等，是临床常用的抗肿瘤药物之一[25]。张静[12]、陈红丽[13]和谢永美[14]分别对壳聚糖载阿霉素、表阿霉素药物缓释系统的抗肿瘤作用进行了研究分析，发现壳聚糖载阿霉素、表阿霉素药物缓释系统不仅具有良好的药物缓释作用，而且对肿瘤细胞具有靶向性抑制作用，是一种良好的抗肿瘤药物缓释系统，具体分析结果见表2。"

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