尽管多西他赛（DX）是一种强效药物，但市场上的配方与诸多副作用相关，而且只能通过静脉注射使用。高端医药纳米技术有望为通过“静脉注射到口服药物”的转换提供重要支持。本研究旨在研制一种经口服给药、靶向叶酸受体的多西他赛纳米脂质体（FA-DX-NLCs），以便在克服生物利用度和毒性问题的同时，促进口服肺癌化疗。基于高压均化和冷冻干燥技术制备的纳米配方，经过多项体外和体内制剂特性的统计分析和评估。结果显示，冷冻干燥后的纳米颗粒形态球形，颗粒大小为183.4±2.13（D90），Pdi为0.358±0.03，% EE为82.41±2.44，% DL为4.41±0.54，ζ电位为-3.3±0.7mv。FA-DX-NLCs的生物利用度显著提高，根据时间曲线下面积（AUC0-t）比较，相较于DX悬液，提高了约27倍。实验中给予的口服FA-DX-NLCs在肺癌临床模型中展现出优异的抗肿瘤功效。肿瘤分期、组织病理学和肿瘤免疫染色显示，与DX悬液相比，FA-DX-NLCs具有更强的抗增殖、凋亡抗转移和抗血管生成的潜力。临床前毒性实验证实，FA-DX-NLCs具有优异的安全性和生物相容性。我们的研究具有极大的转化潜力，可将针对肺癌的多西他赛基于化疗从“医院”转向“家庭”。版权所有©2023 Elsevier B.V.出版。

Despite being potent, the marketed formulations of Docetaxel (DX) are associated with numerous side effects and are meant for intravenous administration. Advanced pharmaceutical nanotechnology has a significant potential to facilitate the 'intravenous (i.v) to oral switch'. The present research work deals with the development of an orally administrable, folate-receptor-targeted Nanostructured lipid carriers (NLCs) of DX (FA-DX-NLCs) for facilitating oral chemotherapy of lung cancer while overcoming the bioavailability and toxicity issues. The nanoformulation prepared to employ high-pressure homogenization and lyophilization, was evaluated and statistically analyzed for various in-vitro and in-vivo formulation characteristics. The lyophilized nanoparticles were observed to be spherical with a particle size of 183.4 ± 2.13 (D90), Pdi of 0.358 ± 0.03, % EE of 82.41 ± 2.44, % DL of 4.41± 0.54 and a zeta potential of -3.3 ± 0.7 mv. The increased oral in-vivo bioavailability of DX was evident from the plasma-concentration area under the time curve (AUC0-t), which was ∼27-fold greater for FA-DX-NLCs as compared to DX suspension. The orally administered FA-DX-NLCs exhibited excellent antitumor efficacy in a pre-clinical model of lung carcinoma. Tumor staging, histopathology, and immunostaining of the tumors suggested greater anti-proliferative, apoptotic, anti-metastatic, and anti-angiogenic potential as compared to DX-suspension. The pre-clinical toxicity studies affirmed the excellent safety and bio-compatibility of FA-DX-NLCs. The research work presents immense translational potential for switching the DX-based chemotherapy for lung cancer from 'hospital to home.'Copyright © 2023. Published by Elsevier B.V.