【摘要】 目的 研究鬼臼毒素固体脂质纳米粒经皮渗透和皮肤贮留情况。方法 采用Franz扩散池测定鬼臼毒素固体脂质纳米粒的经皮渗透速率，扩散池与供给池之间为大鼠或家兔腹部皮肤，扩散池面积为2.92 cm2。在体外透皮试验完结后，取下皮肤，剪碎匀浆，用50%异丙醇生理盐水提取，提取液处理后用HPLC测定药物浓度。结果 制得的鬼臼毒素固体脂质纳米粒包封率平均为95.28%，RSD为2.53% (n=5)，粒径在50～200 nm之间。固体脂质纳米粒作为载体时，鬼臼毒素经大鼠和家兔离体腹部皮肤的平均渗透速率和累积透过量较市售酊剂明显降低，同时药物贮留量较市售酊剂明显提高。结论 鬼臼毒素固体脂质纳米粒具有较强的皮肤靶向性。
【关键词】 鬼臼毒素;固体脂质纳米粒;经皮渗透;皮肤贮留
Abstract:Objective To study in vitro transdermal penetration and retention of podophyllotoxin solid lipid nanoparticles(SLN). Methods The in vitro transdermal penetration of podophyllotoxin from SLN was determined by Franz diffusion cells. Between donor compartment and receptor compartment was abdominal skin of rats or rabbits,the avaiable diffusion area of cells was 2.92 cm2. The sample was analyzed by HPLC after treatment. After in vitro transdermal penetration experiment completed,the skin were taken down from cells,cut and homogenated,then extracted with 50% isopropanolnormal saline. The extracting solution was analyzed by HPLC. Results The encapsulation efficiency of obtained podophyllotoxin solid lipid nanoparticles were 95.28% on average,with RSD was 2.53% (n=5) and diameter between 50～200 nm. When solid lipid nanoparticles as deliverer,the average transdermal rate and cumulative transdermal quantity of podophyllotoxin through rat and rabbit abdominal skin in vitro were significantly lower than marketed tincture,while skin retention quantity of podophyllotoxin in rat and rabbit abdominal skin were significantly higher than marketed tincture. Conclusion Podophyllotoxin SLN had higher local concentration of drug in skin.
Key words:podophyllotoxin; solid lipid nanoparticles; skin penetration; skin retention
鬼臼毒素(podophyllotoxin,POD)亦名足叶草毒素，为小蘖科桃儿七根茎部提取的有效成分，体外药效试验证明能抑制培养的正常人皮肤角质形成细胞和宫颈癌上皮细胞的脱氧核苷掺入和DNA合成，阻碍其分裂和增殖[1]。以鬼臼毒素为主药的制剂在临床已应用多年，其治疗作用已得到肯定。目前临床上广泛使用0.5%鬼臼毒素酊剂治疗尖锐湿疣，多发性浅表性上皮瘤病(如多发性浅表性或浸润性基底细胞上皮瘤，鳞状细胞上皮瘤和基底鳞状细胞上皮瘤)，前上皮瘤性角化病，脂溢性角化、日光性角化和射线角化病，幼年喉头乳头瘤、疣(寻常疣、丝状疣)等疾病[2-4]。但鬼臼毒素酊剂大面积使用时易产生吸收毒性，因此限制了其使用范围。固体脂质纳米粒(solid lipid nanoparticle，SLN)是以固态的天然或合成的脂类如硬脂酸、磷脂、三酰甘油、长饱和脂肪酸等作为药物载体，将药物包裹或夹嵌于类脂核中制成粒径约为50～1 000 nm的粒子，具有体积小、脂溶性大、皮肤靶向性较强[5-6]等优点。以固体脂质纳米粒作为鬼臼毒素载体的研究在国内开展得较多，但在制备过程中均使用了二氯甲烷等有机溶剂，而且对皮肤贮留情况的研究较少[7-10]。本研究采用微乳法制备鬼臼毒素固体脂质纳米粒，避免了有机溶剂的使用，并对其经皮吸收和皮肤贮留情况进行较系统的研究。
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