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负载他莫昔芬和白藜芦醇的固体自纳米乳化纳米平台用于乳腺癌治疗

Solid Self-Nano Emulsifying Nanoplatform Loaded with Tamoxifen and Resveratrol for Treatment of Breast Cancer.

作者信息

Shrivastava Nupur, Parikh Ankit, Dewangan Rikeshwer Prasad, Biswas Largee, Verma Anita Kamra, Mittal Saurabh, Ali Javed, Garg Sanjay, Baboota Sanjula

机构信息

Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.

Pharmaceutical Innovation and Development (PIDG) Group, Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia.

出版信息

Pharmaceutics. 2022 Jul 18;14(7):1486. doi: 10.3390/pharmaceutics14071486.

Abstract

The solid self-nanoemulsifying drug delivery system (s-SNEDDS) is a growing platform for the delivery of drugs via oral route. In the present work, tamoxifen (TAM) was loaded in SNEDDS with resveratrol (RES), which is a potent chemotherapeutic, antioxidant, anti-inflammatory and P-gp inhibitor for enhancing bioavailability and to obtain synergistic anti-cancer effect against breast cancer. SNEDDS were developed using capmul MCM as oil, Tween 80 as surfactant and transcutol-HP as co-surfactant and optimized by central composite rotatable design. Neusilin US2 concentration was optimized for adsorption of liquid SNEDDS to prepare s-SNEDDS. The developed formulation was characterized and investigated for various in vitro and cell line comparative studies. Optimized TAM-RES-s-SNEDDS showed spherical droplets of a size less than 200 nm. In all in vitro studies, TAM-RES-s-SNEDDS showed significantly improved (p ˂ 0.05) release and permeation across the dialysis membrane and intestinal lumen. Moreover, TAM-RES-s-SNEDDS possessed significantly greater therapeutic efficacy (p < 0.05) and better internalization on the MCF-7 cell line as compared to the conventional formulation. Additionally, oral bioavailability of TAM from SNEDDS was 1.63 folds significantly higher (p < 0.05) than that of combination suspension and 4.16 folds significantly higher (p < 0.05) than TAM suspension. Thus, findings suggest that TAM- RES-s-SNEDDS can be the future delivery system that potentially delivers both drugs to cancer cells for better treatment.

摘要

固体自纳米乳化药物递送系统(s-SNEDDS)是一种不断发展的通过口服途径递送药物的平台。在本研究中,他莫昔芬(TAM)被负载于含有白藜芦醇(RES)的SNEDDS中,白藜芦醇是一种有效的化疗药物、抗氧化剂、抗炎剂和P-糖蛋白抑制剂,可提高生物利用度并获得针对乳腺癌的协同抗癌效果。以Capmul MCM为油相、吐温80为表面活性剂、二乙二醇单乙基醚醋酸酯为助表面活性剂开发了SNEDDS,并通过中心复合旋转设计进行优化。优化了Neusilin US2的浓度以吸附液体SNEDDS来制备s-SNEDDS。对所开发的制剂进行了表征,并开展了各种体外和细胞系比较研究。优化后的TAM-RES-s-SNEDDS呈现出尺寸小于200 nm的球形液滴。在所有体外研究中,TAM-RES-s-SNEDDS在透析膜和肠腔中的释放和渗透均有显著改善(p<0.05)。此外,与传统制剂相比,TAM-RES-s-SNEDDS在MCF-7细胞系上具有显著更高的治疗效果(p<0.05)和更好的内化作用。另外,TAM从SNEDDS的口服生物利用度比联合混悬液显著高1.63倍(p<0.05),比TAM混悬液显著高4.16倍(p<0.05)。因此,研究结果表明TAM-RES-s-SNEDDS可能成为未来的递送系统,有潜力将两种药物都递送至癌细胞以实现更好的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8700/9318459/7ff7a9a87f2c/pharmaceutics-14-01486-g001.jpg

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