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用于改善乳腺癌药物口服递送的纳米乳剂和固体纳米乳剂:制剂、评价及比较研究。

Nanoemulsion and Solid Nanoemulsion for Improving Oral Delivery of a Breast Cancer Drug: Formulation, Evaluation, and a Comparison Study.

作者信息

Tarik Alhamdany Anas, Saeed Ashti M H, Alaayedi Maryam

机构信息

Department of Pharmaceutics, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq.

Department of Pharmaceutics, College of Pharmacy, University of Kerbala, Kerbala, Iraq.

出版信息

Saudi Pharm J. 2021 Nov;29(11):1278-1288. doi: 10.1016/j.jsps.2021.09.016. Epub 2021 Oct 8.

Abstract

Letrozole (LZ) is an aromatase inhibitor, which inhibits the formation of estrogens from androgens. Nanoemulsion is a liquid emulsion formulation utilized to increase solubility, bioavailability, and drug delivery to cancer cells. This study aims to improve LZ oral delivery through formulating solid nanoemulsion (SNE). Peppermint oil, tween 80, and transcutol P were used as an oil, surfactant, and co-surfactant, respectively. The optimized nanoemulsion (NE-3) was then incorporated into solid polyethylene glycol (PEG) to formulate (SNE). The optimized (NE-3), SNE-2, and the available marketed tablet have been compared. The optimized (NE-3) was selected according to specific parameters of optimum small nano-size 80 nm, PDI of 0.181, the zeta potential of-98.2, high transmittance (99.78%), optimum pH (5.6), a high percent of LZ content (99.03 ± 1.90), the relatively low viscosity of 60.2 mPa.s, and a rapid release of LZ within 30 min. NE-3 was selected to be formulated as SNE. LZ's best release rate was 80% in 5 min with a content homogeneity of 99.85 ± 0.04 for SNE-2. Zero-order kinetics is determined to have the greatest R values. Field emission scanning electron microscopy (FE-SEM) detected that SNE-2 was (36.75-96.64 nm) with a spherical form and no adhesion or aggregation. FT-IR showed no significant variations in position and shape of the absorption peaks between the pure drug and optimal formulation diagrams. This novel nanoemulsion technology aids in improving the solubility of poorly water-soluble drugs, particularly the SNE delivery method, which has a higher in-vitro release rate and expiration date of LZ than others.

摘要

来曲唑(LZ)是一种芳香酶抑制剂,可抑制雄激素转化为雌激素。纳米乳剂是一种液体乳剂制剂,用于提高溶解度、生物利用度以及向癌细胞的药物递送。本研究旨在通过制备固体纳米乳剂(SNE)来改善LZ的口服给药。分别使用薄荷油、吐温80和二乙二醇单乙醚作为油相、表面活性剂和助表面活性剂。然后将优化后的纳米乳剂(NE-3)加入固体聚乙二醇(PEG)中制成(SNE)。对优化后的(NE-3)、SNE-2和市售片剂进行了比较。根据最佳小纳米尺寸80nm、PDI为0.181、ζ电位为-98.2、高透光率(99.78%)、最佳pH值(5.6)、高LZ含量百分比(99.03±1.90)、相对较低的粘度60.2mPa·s以及LZ在30分钟内快速释放等特定参数选择了优化后的(NE-3)。选择NE-3制成SNE。SNE-2中LZ的最佳释放率在5分钟内为80%,含量均匀度为99.85±0.04。确定零级动力学具有最大的R值。场发射扫描电子显微镜(FE-SEM)检测到SNE-2为(36.75-96.64nm),呈球形,无粘附或聚集。傅里叶变换红外光谱(FT-IR)显示纯药物和最佳制剂图谱之间吸收峰的位置和形状没有显著变化。这种新型纳米乳剂技术有助于提高难溶性药物的溶解度,特别是SNE递送方法,其体外释放率和LZ的有效期比其他方法更高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7637/8596290/896f98879bd2/gr1.jpg

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