用于肺部疾病及其他疾病的 Nintedanib 先进给药策略:全面回顾

IF 3.4 4区 医学 Q2 PHARMACOLOGY & PHARMACY AAPS PharmSciTech Pub Date : 2024-07-01 DOI:10.1208/s12249-024-02869-9
Dhruti Thakkar, Sanskriti Singh, Sarika Wairkar
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引用次数: 0

摘要

作为肺纤维化的主要治疗药物,宁替达尼因其多方面的潜力而备受关注。作为一种酪氨酸激酶抑制剂,宁替达尼可抑制多种信号受体,包括内皮生长因子受体(VEGFR)、血小板衍生生长因子受体(PDGFR)和成纤维细胞生长因子受体(FGFR),并最终抑制成纤维细胞的增殖和分化。因此,除了肺部疾病外,宁替达尼还被广泛用于癌症和肝纤维化等其他疾病的治疗。在商业上,宁替尼以软胶囊的形式供应,用于治疗特发性肺纤维化。由于它的口服生物利用度很低(4.7%),因此给药剂量较大,如 100-150 毫克,可能会引起胃肠道刺激和肝毒性问题。文章首先探讨了宁替尼的作用机制,阐明了其在支配纤维化过程的细胞通路中的复杂相互作用。文章还强调了宁替尼的药代动力学、临床试验启示以及传统制剂的局限性。文章主要关注以纳米粒子为基础的载体(如脂质体-外泌体混合体、纳米液晶、盘状聚合物和磁性系统)的新兴前景,这些载体为优化药物靶向、解决药效问题和减少不良反应提供了大有可为的途径。然而,这些给药系统都尚未商业化,还需要进一步研究,以确保在临床环境中的安全性和有效性。不过,随着研究的不断深入,这些先进的给药系统有望彻底改变各种纤维化疾病和癌症的治疗格局,从而改善患者的治疗效果和生活质量。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Advanced Delivery Strategies of Nintedanib for Lung Disorders and Beyond: A Comprehensive Review.

Nintedanib, a primary treatment for lung fibrosis, has gathered substantial attention due to its multifaceted potential. A tyrosine kinase inhibitor, nintedanib, inhibits multiple signalling receptors, including endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR) and ultimately inhibits fibroblast proliferation and differentiation. Therefore, nintedanib has been studied widely for other ailments like cancers and hepatic fibrosis, apart from lung disorders. Commercially, nintedanib is available as soft gelatin capsules for treatment against idiopathic pulmonary fibrosis. Since it has very low oral bioavailability (4.7%), high doses of a drug, such as 100-150 mg, are administered, which can cause problems of gastrointestinal irritation and hepatotoxicity. The article begins with exploring the mechanism of action of nintedanib, elucidating its complex interactions within cellular pathways that govern fibrotic processes. It also emphasizes the pharmacokinetics of nintedanib, clinical trial insights, and the limitations of conventional formulations. The article mainly focuses on the emerging landscape of nanoparticle-based carriers such as hybrid liposome-exosome, nano liquid crystals, discoidal polymeric, and magnetic systems, offering promising avenues to optimize drug targeting, address its efficacy issues and minimise adverse effects. However, none of these delivery systems are commercialised, and further research is required to ensure safety and effectiveness in clinical settings. Yet, as research progresses, these advanced delivery systems promise to revolutionise the treatment landscape for various fibrotic disorders and cancers, potentially improving patient outcomes and quality of life.

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来源期刊
AAPS PharmSciTech
AAPS PharmSciTech 医学-药学
CiteScore
6.80
自引率
3.00%
发文量
264
审稿时长
2.4 months
期刊介绍: AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.
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