酸敏感聚合物纳米载体用于阿达帕林经皮给药的研究

发布时间：2018-10-12 17:28

【摘要】：痤疮是一种非常常见的皮肤疾病，对大多数青少年均有不同程度的影响。正常皮肤表面的pH均值约为5.5，而痤疮皮肤表面的pH值比正常皮肤表面的pH值偏低，低至4.0。阿达帕林是目前广泛应用于痤疮经皮治疗的第三代维甲酸药物，但是，目前阿达帕林市售剂型往往伴随浓度和基质相关的皮肤刺激性，导致患者顺应性较差。将药物包载于酸敏感的聚合物载体中不仅可有效避免药物在给药皮肤部位的大量释放，还可利用痤疮皮肤特殊的酸性微环境对药物进行控制释放，从而减少对皮肤的刺激性。本文采用纳米沉淀方法将阿达帕林包载于酸敏感聚合物Eudragit EPO中，经高效液相色谱法测得酸敏感阿达帕林载药纳米粒的载药量为3.5±0.3%(w/w)。经过动态光散射证实得到的纳米粒粒径为125.8±3.5nm，呈球状形态，同时表面带有正电荷（Zeta电位18.4±2.9mV）。通过X射线衍射(XRD)、差热分析(DTA)以及傅里叶变换红外光谱(FTIR)研究了药物与聚合物之间的相互作用：(1)聚合物的疏水骨架与药物芳环之间的疏水作用；(2)药物羧基与聚合物氨基间形成氢键。药物释放实验证实了制备的酸敏感阿达帕林载药纳米粒在较低的pH条件(pH4.0)下，，药物的释放量显著高于相对较高的pH条件(pH5.0, pH6.0)下。在以聚二甲基硅氧烷膜为膜材料的渗透实验中，基于阿达帕林载药纳米粒水混悬液的高热力学活性，其稳态渗透速率统计学意义上显著大于对照组（相同药物浓度的阿达帕林的二乙二醇单乙基醚Transcutol溶液）。在以完整猪皮肤为膜材料的渗透实验中，利用角质剥离技术证明阿达帕林载药纳米粒水混悬液与对照组（相同药物浓度的阿达帕林的Transcutol溶液）递送进入角质层的药物的量无显著差别。总之，本文证实了酸敏感阿达帕林载药纳米粒可以显著提高药物的经皮递送效率，减少皮肤刺激性，提高药物疗效。
[Abstract]:Acne is a very common skin disease that affects most adolescents to varying degrees. The average value of pH on normal skin surface was about 5.5, while the pH value of acne skin surface was lower than that of normal skin surface, which was as low as 4.0. Adalparine is the third generation of retinoic acid which is widely used in the percutaneous treatment of acne. However, at present, the dosage form of Adalparine is often accompanied by skin irritation associated with concentration and matrix, which leads to poor compliance of patients. Drug encapsulation in acid-sensitive polymer carrier can not only effectively avoid a large amount of drug release in the skin, but also control the release of the drug by using the special acidic microenvironment of acne skin, thus reducing the irritation to the skin. In this paper, the method of nanoprecipitation was used to encapsulate adalepalin in acid-sensitive polymer Eudragit EPO. The drug loading capacity of acid-sensitive adalin-loaded nanoparticles was 3.5 卤0.3% (w / w) by high performance liquid chromatography (HPLC). The particle size is 125.8 卤3.5 nm, which is spherical and has a positive surface charge (Zeta potential 18.4 卤2.9mV). The interaction between drug and polymer was studied by (XRD), differential thermal analysis (DTA) and Fourier transform infrared spectroscopy (FTIR). (1) the hydrophobic interaction between the hydrophobic skeleton of polymer and the aromatic ring of the drug; (2) hydrogen bond was formed between carboxyl group and amino group. Drug release experiments confirmed that the drug release of acid-sensitive adalin-loaded nanoparticles at lower pH condition (pH4.0) was significantly higher than that under relatively high pH condition (pH5.0, pH6.0). In the permeation experiment of polydimethylsiloxane membrane, based on the high thermodynamic activity of water suspension of adalin-loaded nanoparticles, The steady-state osmotic rate was significantly higher than that of the control group (diethylene glycol monoethyl ether Transcutol solution with the same drug concentration). In the permeation experiment using intact porcine skin as membrane material, The keratinocyte stripping technique showed that there was no significant difference in the amount of drugs delivered into the keratinocytes between the adalin-loaded nanoparticles water suspension and the control group (the Transcutol solution of the same drug concentration). In conclusion, it has been proved that acid-sensitive adalin-loaded nanoparticles can significantly improve the transdermal delivery efficiency, reduce skin irritation and improve drug efficacy.
【学位授予单位】：天津大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R96

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