Different release properties and targeting effects of sustained-release drugs for the treatment of gastric cancer

doi:10.3969/j.issn.2095-4344.2013.08.025

Abstract

Abstract:

BACKGROUND: The delivery system of chemotherapy drugs can improve the therapeutic effect of chemotherapy drugs on gastric cancer, and it is a hot spot of the research of drug materials.
OBJECTIVE: To evaluate release properties and targeting effects of sustained-release drugs for the treatment of gastric cancer.
METHODS: The 5-fluorouracil polylactic acid sustained-release drugs, 5-fluorouracil chitosan sustained-release drugs, nano-activated carbon mitomycin sustained-release drugs and chitosan cisplatin sustained-release drugs were prepared through different methods. Sustained-release performance and characteristics of the drugs above were detected, and the targeting effects and therapeutic effect of the drugs on gastric cancer were identified.
RESULTS AND CONCLUSION: The 5-fluorouracil polylactic acid sustained-release drugs, 5-fluorouracil chitosan sustained-release drugs, nano-activated carbon mitomycin sustained-release drugs and chitosan cisplatin sustained-release drugs have good sustained-release properties which can prolong the effective time of drugs on tumor tissues, help the chemotherapy drugs play a stronger inhibition and killing effect on gastric cancer cells, improve prognosis and prolong the survival of patients with gastric cancer. In addition, the application of peritoneal perfusion of chemotherapy drugs can further improve the killing effect of chemotherapy drugs on gastric cancer tissues.

Key words: biomaterials, academic discussion of biomaterials, gastric cancer, sustained-release, drugs, 5-fluorouracil, mitomycin, cisplatin, polylactic acid, chitosan, activated carbon, chitosan

CLC Number:

R318

Zhang Wei, Kang Hai-han, Zhang Yong-lei, Kong Ye, Hua Ya-wei. Different release properties and targeting effects of sustained-release drugs for the treatment of gastric cancer[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(8): 1481-1488.

Figures/Tables 7

对5-氟尿嘧啶缓释药物系统的肿瘤靶向作用进行研究分析，发现由腹腔灌注化疗缓释药物而导致化疗药物分布浓度由高到低依次为癌周淋巴结、胃癌组织、腹膜、胃黏膜、大网膜、小网膜，而由静脉滴注化疗缓释药物而导致化疗药物分布浓度由高到低依次为癌周淋巴结、胃癌组织、胃黏膜、腹膜、大网膜、小网膜。腹腔灌注化疗缓释药物使局部组织的药物浓度更高。 2.2 丝裂霉素药物载体缓释系统治疗胃癌的药物缓释特性丝裂霉素是一种广谱抗肿瘤药物，属于细胞周期非特异性药物，固体状态时性质稳定，在酸性和碱性溶液中容易失去活性，易溶于水、甲醇和丙酮等有机溶剂，微溶于苯、乙醚和四氯化碳，不溶于石油醚。静脉注射时初始相半衰期为17 min，终止相半衰期为50 min，经肝脏代谢，肾脏排出体外。活性碳吸附丝裂霉素具有较高的吸附性和良好的缓释功能，以及良好的淋巴靶向性，毒副作用小[33]。直径较小的缓释药物可以选择性地进入淋巴管，聚集到区域淋巴结内，而较大直径的缓释药物则可以被乳糜斑摄入[34-35]。活性碳作为载体吸附丝裂霉素缓释药物已被证明具有良好的抗肿瘤活性[36-37]。张李[20]研究分析了纳米活性碳吸附丝裂霉素C对胃癌的靶向作用，发现纳米活性碳吸附丝裂霉素C对胃癌组织周围的淋巴结具有更强的靶向性。具体分析结果见表4。张浩[19]对活性碳吸附丝裂霉素缓释药物的药物缓释特性以及抗肿瘤作用进行了分析，实验获得活性碳吸附丝裂霉素缓释药物微球的粒径为(60.0± 20.0) nm，载药量为20.0%，具有良好的药物缓释作用，可持续缓释药物28 d，累积释放药量70.1%。对胃癌组织的抑制作用明显高于单纯应用丝裂霉素，而对正常组织的损伤作用明显小于单纯应用丝裂霉素，能够有效抑制胃癌的转移和复发。"

文章研究显示纳米活性炭吸附丝裂霉素对胃癌有较强的靶向治疗作用，尤其是对癌组织周围的淋巴靶向作用更强，其次是肠系膜和腹腔液，而血浆中的药物浓度很低。纳米活性炭吸附丝裂霉素对胃癌的治疗具有肿瘤高度选择性，采用腹腔灌注药物的给药途径，缩短了药物到达肿瘤的时间，延长了药物与肿瘤的作用时间，维持腹腔内较高的有效药物浓度，明显提高了药物对胃癌组织的抑制和杀伤作用。因此，纳米活性炭吸附丝裂霉素缓释药物是一种较为理想治疗胃癌的缓释药物系统，具有广泛应用的可能性。 2.3 几丁糖-顺铂药物载体缓释系统治疗胃癌的药物缓释特性顺铂是临床常用的化疗药物之一，属于细胞周期非特异性药物，具有细胞毒性，可抑制肿瘤细胞的DNA复制过程，并损伤其细胞膜结构，从而发挥抗肿瘤的作用，具有广谱抗肿瘤的作用。但单纯应用顺铂治疗胃癌，会产生骨髓抑制、肾脏毒性以及神经毒性等各种毒副作用，因此，应用时常采用缓释药物材料负载化疗药物。几丁糖是甲壳素经浓碱水脱去乙酰基后生成的阳离子水溶性聚合物，其分子内的活性基团亚胺基，可以与含双官能团的醛或酸酐药物化学偶联，使化疗药物大量分布于偶联结构内，发挥缓释抗肿瘤的作用[38]。几丁糖能够溶于酸性溶液中，具有良好的生物黏附性、良好的组织相容性、良好的自然降解性和较强的吸附性能，是一种较为理想的缓释药物载体[39-42]。朱共元[21]和魏玉亮[22]分别对几丁糖-顺铂药物载体缓释系统的特征以及对胃癌的治疗作用进行了研究分析，发现几丁糖-顺铂缓释药膜能够持续释放药物7 d，具有良好的药物缓释性能，同时具有较强的胃癌组织抑制作用。对几丁糖-顺铂药物缓释系统进行体外实验研究发现，与单纯药物顺铂、几丁糖相比较，几丁糖-顺铂缓释药膜对肿瘤组织的作用时间更长，并且药物浓度明显高于单纯药物应用时的浓度，对肿瘤组织的抑制作用也明显高于单纯药物的应用，具体结果见表5-7。"

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