用于治疗非小细胞肺癌的阿法替尼脂质体的制备与包封率的测定

Formulation and Efficacy of Liposome-encapsulated Afatinib for Therapy of Non-small Cell Lung Cancer

背景与目的阿法替尼是针对非小细胞肺癌及继发性耐药研发的第二代不可逆表皮生长因子受体抑制剂,目前仅停留在口服给药方式,其生物利用度低,不良反应较多。本研究旨在制备新型药物传递系统-阿法替尼脂质体,并建立包封率的测定方法。方法 4种不同方法制备阿法替尼脂质体,通过对比包封率和粒径确定最佳制备工艺。结果经验证可采用葡聚糖凝胶微柱离心法纯化脂质体,并通过紫外分光光度法测定脂质体的包封率。不同制备方法中硫酸铵梯度法制备的脂质体,包封率约为90.73%,平均粒径为108.6 nm。结论硫酸铵梯度法制备阿法替尼脂质体包封率高、粒径小,紫外分光光度法用来测定脂质体的包封率简单易行、准确度高。

Background and objective Afatinib, a second-generation irreversible epidermal growth factor inhibitor receptor for the development of non-small cell lung cancer and secondary drug resistance, has low bioavailability and adverse reactions due to current oral administration. The aim of this study was to prepare a novel drug delivery system, afatinib lipo- some, and to establish a method for the determination of encapsulation efficiency. Methods Four different preparation meth- ods were used to prepare afatinib liposomes, and the optimal preparation process was determined by comparing the encapsula- tion efficiency and particle size. Results It has been verified that sephadex microcolumn centrifugation can be used to purify afatinib liposomes, and UV spectrophotometry can be employed to determine the entrapment efficiency ofliposomes. Among different preparation methods, the encapsulation efficiency of afatinib liposomes prepared by ammonium sulfate gradient method was 90.73% and the average particle size was 108.6 nm. Conclusion Ammonium sulfate gradient method can be suc- cessfully applied to prepare afatinib liposomes that performed higher encapsulation efficiency and smaller particle size. The UV spectrophotometry employed to determine the liposome encapsulation efficiency was easy operation and with high accuracy.