新型"硬核软膜"结构纳米缓释制剂对瑞戈非尼的载药实验研究

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中文摘要：目的建立的一种新型的、以聚丁二酰亚胺(polysuccinimide，PSI)与羟基磷灰石(hydroxyapatite，HAP)为基本构成成分的纳米缓释递药系统PSI-HAP，并对抗肿瘤药物瑞戈非尼的载药释药能力进行研究。方法本实验合成了制剂所需辅料HAP与PSI;建立了紫外分光光度法对瑞戈非尼的含量进行检测;采用单因素结合响应面曲线法(box-behnken design，BBD)对不同方式制备的瑞戈非尼纳米缓释递药系统的处方与工艺进行考察;对制剂的载药与释药能力、制剂形态，Zeta电位与粒径等制剂学性质进行了考察。采用荧光染料尼罗红对载药PSI-HAP纳米粒进行标记，通过小动物活体成像技术观察纳米粒在小鼠体内的分布情况。结果经紫外扫描确定瑞戈非尼检测波长为264nm，标准曲线为A=94。461p+0。030 4，r2=0。999 8，精密度准确度实验显示，瑞戈非尼在0。002～0。02 mg·mL-1内线性关系良好;BBD确定采用乳液法制备瑞戈非尼PSI-HAP制剂处方为药物浓度7。28 mg·mL-1，HAP与药物质量比为0。63，PSI与HAP质量比为3。93;体外释放实验结果显示，该递药系统具备pH敏感性，在pH值大于7时，药物会得到较为完全的释放。扫描电镜(SEM)结果显示，制剂粒径在300 nm上下，Zeta电位为负，与人体生物膜荷电性相同。体内分布实验结果显示，PSI-HAP制剂可显著延长制剂在动物体内的滞留时间。结论本实验建立的新型纳米递药系统的制备工艺极其简单，易于灭菌，无需高压、挤压、过滤等工艺即可制备出粒径均一的纳米粒子，药物释放平稳且具备pH敏感性，PSI与纳米HAP都具备抗肿瘤细胞增殖的作用，非常适用于抗肿瘤药物的体内递送。

外文标题：A Novel Nano Sustain-Released Drug Delivery System Encapsulated Regorafenib with a Hard Core-Soft Film Structure

外文摘要：OBJECTIVE To establish a nano sustained release drug delivery system polysuccinimide(PSI)and hydroxyapatite(HAP)with a hard core-soft coating structure and study the delivery of anti-tumor drug regorafenib.METHODS HAP and PSI were synthesize in the article.The optimal formulation and preparation process of the regorafenib-PSI-HAP was determined by single factor analysis and the box-behnken design(BBD)response surface method.The encapsulation efficiency,drug loading captivity,drug release in vitro,particle size and distribution,Zeta potential and SEM images of regorafenib-PSI-HAP were examined.RESULTS The UV spectrophotometry results showed that the maximum absorption wave of the regorafenib was at 264 nm,the stand curve was A=94.461p+0.0304,r2=0.999 8.Meanwhile,between the 2-20 μg·mL-1 of the regorafenib solutions possessed a good linear relationship at this wave.The optimal formulation prepared using MEM detected by BBD was that the concentration of rego-rafenib was 7.28 mg·mL-1,the mass ratio of HAP to regorafenib was 0.63,and the mass ratio of PSI to HAP was 3.93.The in vitro drug release test showed that PSI-HAP exhibited pH-sensitive drug release,the regorafenib-PSI-HAP can be released totally above pH 7 solution.The PSD was around 300 nm,and Zeta potential was between-10 and-17 mV which was similar to the human cell mem-brane.CONCLUSION The proposed drug delivery system can be integrated into non-agglomerated spherical nanoparticles of uniform size through a facile preparation process.The particles are easy to sterilize,and large-scale production may be achieved easily.The drug release of PSI-HAP is pH sensitive and stable.Both PSI and nano HAP possess the effect of anti-tumor cell proliferation which is very suitable for the delivery of anti-tumor drugs such as regorafenib in vivo.

外文关键词：

"hard core-soft film"structurenano sustained-release drug delivery systemregorafenibpH sensitivitybox-behnken design response surface method

作者：

刘丹、王宏远、王晶华、范兴君、王强、刘佳维、佟雷、翟凤国、于凤波

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作者单位：

牡丹江医学院,黑龙江牡丹江 157011

关键词：

"硬核软膜"结构纳米缓释瑞戈非尼 pH敏感单因素结合响应面曲线法

基金：

中国博士后科学基金面上项目广东省中医药局科研项目黑龙江省教育厅省属高等学校基本科研业务费科研项目牡丹江医学院博士科研启动基金

项目编号：

2021M692734202214472019-KYYWFMY-00032021-MYBSKY-046

出版年：

2024

DOI：

10.11669/cpj.2024.04.004

中国药学杂志

中国药学会

中国药学杂志

CSTPCD北大核心

影响因子：0.957

ISSN：1001-2494

年,卷(期)：2024.59(4)

参考文献量21