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用于治疗基底细胞癌的光动力疗法中的纳米结构脂质载体。

Nanostructured lipid carrier in photodynamic therapy for the treatment of basal-cell carcinoma.

作者信息

Qidwai Afreen, Khan Saba, Md Shadab, Fazil Mohammad, Baboota Sanjula, Narang Jasjeet K, Ali Javed

机构信息

a Department of Pharmaceutics , Faculty of Pharmacy, Jamia Hamdard , New Delhi , India .

b Department of Pharmaceutical Technology , School of Pharmacy, International Medical University (IMU) , Kuala Lumpur , Malaysia , and.

出版信息

Drug Deliv. 2016 May;23(4):1476-85. doi: 10.3109/10717544.2016.1165310. Epub 2016 Apr 5.

Abstract

Topical photodynamic therapy (PDT) is a promising alternative for malignant skin diseases such as basal-cell carcinoma (BCC), due to its simplicity, enhanced patient compliance, and localization of the residual photosensitivity to the site of application. However, insufficient photosensitizer penetration into the skin is the major issue of concern with topical PDT. Therefore, the aim of the present study was to enable penetration of photosensitizer to the different strata of the skin using a lipid nanocarrier system. We have attempted to develop a nanostructured lipid carrier (NLC) for the topical delivery of second-generation photosensitizer, 5-amino levulinic acid (5-ALA), whose hydrophilicity and charge characteristic limit its percutaneous absorption. The microemulsion technique was used for preparing 5-ALA-loaded NLC. The mean particle size, polydispersity index, and entrapment efficiency of the optimized NLC of 5-ALA were found to be 185.2 ± 1.20, 0.156 ± 0.02, and 76.8 ± 2.58%, respectively. The results of in vitro release and in vitro skin permeation studies showed controlled drug release and enhanced penetration into the skin, respectively. Confocal laser scanning microscopy and cell line studies respectively demonstrated that encapsulation of 5-ALA in NLC enhanced its ability to reach deeper skin layers and consequently, increased cytotoxicity.

摘要

局部光动力疗法(PDT)因其操作简单、患者依从性高以及残余光敏性局限于应用部位等特点,是治疗基底细胞癌(BCC)等恶性皮肤疾病的一种有前景的替代方法。然而,光敏剂渗透到皮肤不足是局部光动力疗法主要关注的问题。因此,本研究的目的是使用脂质纳米载体系统使光敏剂渗透到皮肤的不同层次。我们试图开发一种纳米结构脂质载体(NLC)用于第二代光敏剂5-氨基乙酰丙酸(5-ALA)的局部递送,5-ALA的亲水性和电荷特性限制了其经皮吸收。采用微乳技术制备负载5-ALA的NLC。5-ALA优化后的NLC的平均粒径、多分散指数和包封率分别为185.2±1.20、0.156±0.02和76.8±2.58%。体外释放和体外皮肤渗透研究结果分别表明药物释放得到控制且皮肤渗透增强。共聚焦激光扫描显微镜和细胞系研究分别证明,5-ALA包封在NLC中增强了其到达更深皮肤层的能力,从而增加了细胞毒性。

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