丙烯酸酯-PEG400复合薄膜对胰岛素的体外控释研究

In vitro Study on Acrylate-PEG400 Composite Membranes for Controlled Release of Insulin

目的:在胰岛素非注射给药研究中,经皮给药系统凭借其独特的优势,已成为近年来医药领域的研发重点。控释膜的研究是经皮给药系统中一个重要组成部分,然而涉及胰岛素通过控释膜释放的研究报道不多。本实验室通过紫外光催化技术合成出一种丙烯酸酯-PEG复合薄膜作为胰岛素控释膜。本实验目的在于考察该复合薄膜在24小时内对胰岛素的体外控释作用,从而为胰岛素经皮给药制剂的基础研究作出贡献。方法:通过紫外光固化方法合成丙烯酸酯-PEG400复合薄膜,通过HPLC的方法考察丙烯酸酯-PEG400复合薄膜对不同浓度胰岛素溶液的控释作用,通过比较薄膜对不同浓度胰岛素溶液的累积渗透量及渗透速率等参数,研究薄膜对胰岛素的控释规律。结果:实验数据显示:丙烯酸酯-PEG复合薄膜对3.0 mg/mL,6.0 mg/mL,9.0 mg/mL这三种不同浓度胰岛素控释曲线的相关因子分别为:0.9921,0.9950,0.9964。相关因子均大于0.99,表明该薄膜能很好的控制胰岛素溶液实现线性释放。经计算,薄膜对3.0 mg/mL,6.0 mg/mL,9.0 mg/mL这三种浓度胰岛素的累积渗透量分别为:266.69μg/cm2,343.65μg/cm2,460.10μg/cm2。渗透速率分别为:9.24μg·cm-2·h-1,13.40μg·cm-2·h-1,19.04μg·cm-2·h-1。以上两组数据表明,薄膜对胰岛素的累积渗透量及渗透速率随胰岛素浓度的增加而增大。结论:通过实验结果我们可以看出,丙烯酸酯-PEG复合薄膜能控制不同浓度的胰岛素溶液以恒定速率释放,通过对比薄膜对各浓度胰岛素的累积渗透量及渗透速率等参数,发现该薄膜对胰岛素的释放速率受胰岛素浓度调节,具体表现为随胰岛素浓度的增加而增加。因此该薄膜不仅可以稳定控制胰岛素实现零级释放,而且可以通过调节胰岛素浓度实现调节胰岛素释放速率的目的。由此可以看出,该薄膜是一种理想的胰岛素控释膜。同时本实验作为胰岛素控释膜的基础研究,也为日后以该薄膜为控释膜的胰岛素经皮给药制剂的研发打下了坚实的基础。

Objective： Among non-injection drug administration systems, transdermal drug delivery system （TDDS） has become the focus in the field of pharmaceutical research and development for its unique advantages. The study on controlled release membrane is an important component in TDDS research. However, there are few reports related to controlling insulin to release through controlled release membranes. In our laboratory, a novel acrylate-PEG400 composite membrane, which is a controlled release membrane for insulin, was synthesized by UV curing method. The aim of this experiment was to study the in vitro controlled release properties of this membrane for insulin in 24 hours, and to make a contribution to the basic research of insulin TDDS. Methods： Acrylate-PEG400 membranes were synthesized by UV curing method. Then, the controlled release properties of acrylate-PEG membranes for insulin in different concen trations were analyzed by HPLC method. The controlled release rule was studied by comparing the release properties of insulin solution in different concentrations, including cumulative permeation value and permeation rate. Results： The experimental data showed that, for three insulin solutions in different concentrations including 3.0 mg/mL, 6.0 mg/mL, 9.0 mg/mL, the related factors of controlled release curve were as follows： 0.9921, 0.9950, 0.9964. The data above indicated that this membrane could control insulin liner release well, for all the related factors were above 0.99. After calculating, the cumulative permeation values and permeation rates for three different insulin solutions, the concentrations of which were 3.0 mg/mL, 6.0 mg/mL, 9.0 mg/mL, were obtained. The cumulative permeation values were as follows： 266.69 μg/cm2 343.65 μg/cm2, 460.10 μg/cm2. And the permeation rates were as follows： 9.24 μg·cm-2 ·h-1, 13.40μg·cm-2 ·h-1, 19.04μg·cm-2 ·h-1. From these two sets of data, a conclusion could be inferred that, the release rate of insulin increased by the increase of the concentration of insulin. Conclusion： From the experimental results we could see that, the acrylate-PEG400 membranes controlled insulin to release in constant rate in vitro. After comparing the release properties of insulin including cumulative permeation value and permeation rate, a rule was found that the release rate of insulin through the acrylate-PEG400 membrane was adjustable. The specific performance of this rule was that, the release rate of insulin increased by the he increase of the concentration of insulin. Thus, this membrane could not only control insulin zero release, but also control insulin to release in a certain rate by adjusting the concentration of insulin to an appropriate proportion, So the acrylate-PEG400 membrane was an ideal controlled release membrane for insulin. This study was a basic research of controlled release membrane for insulin, which would establish a foundation for the research and development of insulin TDDS in future.