A novel fluoride anion modified gelatin nanogel system for ultrasound-triggered drug release.
A novel fluoride anion modified gelatin nanogel system for ultrasound-triggered drug release.
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DOI：
10.18433/j3988j
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发表时间：
2008-12
期刊：
影响因子：
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通讯作者：
Daocheng Wu;M. Wan
中科院分区：
文献类型：
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作者：
Daocheng Wu;M. Wan
目的控制药物释放，特别是肿瘤靶向药物释放仍然是一个巨大的挑战。本文制备了一种新型氟化物阴离子修饰明胶纳米凝胶体系，并对其超声触发药物释放特性进行了研究。方法采用氟离子与硫酸钠共沉淀法制备氟离子修饰阿霉素明胶纳米凝胶（ADM-GNMF）。采用高效液相色谱法测定抗肿瘤药物阿霉素（ADM）的负载率和包封率。采用电子显微镜和光相关光谱法测定了ADM-GNMF的大小和形状。采用设计的亚微米粒度分析仪和超声发生器、超声发生器、自动进样器和高效液相色谱组成的测量装置，测量超声前后ADM-GNMF的粒度分布和药物释放效率。结果ADM-GNMF在溶液中稳定，平均直径为46+/-12 nm；阿霉素包封率为87.2%，装药率为6.38%。超声触发的药物释放和尺寸变化在频率为20 kHz、功率密度为0.4w/cm2、持续时间为1~2 min时最有效。在此超声触发条件下，ADM-GNMF中51.5%的药物在1~2 min内释放，ADM-GNMF的大小在超声作用1~2 min内由46 +/- 12 nm变为1212 +/- 35 nm，超声停止作用2~3 min后恢复到原来的大小。相比之下，ADM-GNMF中8.2%的药物在不超声的情况下在2~3 min内释放，仅发现可忽略不计的尺寸变化。结论ADM-GNMF系统在超声作用下有效释放包膜药物，为肿瘤或其他疾病的靶向治疗提供了一种新的、有前景的药物控制释放系统。
PURPOSE Controlled drug release, especially tumor-targeted drug release, remains a great challenge. Here, we prepare a novel fluoride anion-modified gelatin nanogel system and investigate its characteristics of ultrasound-triggered drug release. METHODS Adriamycin gelatin nanogel modified with fluoride anion (ADM-GNMF) was prepared by a modified co-precipitation method with fluoride anion and sodium sulfate. The loading and encapsulation efficiency of the anti-neoplastic agent adriamycin (ADM) were measured by high performance liquid chromatography (HPLC). The size and shape of ADM-GNMF were determined by electron microscopy and photo-correlation spectroscopy. The size distribution and drug release efficiency of ADM-GNMF, before and after sonication, were measured by two designed measuring devices that consisted of either a submicron particle size analyzer and an ultrasound generator as well as an ultrasound generator, automatic sampler, and HPLC. RESULTS The ADM-GNMF was stable in solution with an average diameter of 46+/-12 nm; the encapsulation and loading efficiency of adriamycin were 87.2% and 6.38%, respectively. The ultrasound-triggered drug release and size change were most efficient at a frequency of 20 kHz, power density of 0.4w/cm2, and a 1~2 min duration. Under this ultrasound-triggered condition, 51.5% of drug in ADM-GNMF was released within 1~2 min, while the size of ADM-GNMF changed from 46 +/- 12 nm to 1212 +/- 35 nm within 1~2 min of sonication and restored to its previous size in 2~3 min after the ultrasound stopped. In contrast, 8.2% of drug in ADM-GNMF was released within 2~3 min without sonication, and only negligible size changes were found. CONCLUSIONS The ADM-GNMF system efficiently released the encompassed drug in response to ultrasound, offering a novel and promising controlled drug release system for targeted therapy for cancer or other diseases.