伊立替康和地塞米松前药共载脂质体治疗乳腺癌

IF 10.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release Pub Date : 2025-07-07 DOI:10.1016/j.jconrel.2025.114017

Mei Chen , Hongbing Liu , Mengqi Xiu , Muse Ji , Dongmei Shi , Jingxin Gou , Haibing He , Tian Yin , Xing Tang , Guoliang Chen , Yu Zhang

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引用次数: 0

摘要

癌症是一项重大的全球健康挑战，对人类健康和生命产生严重影响。虽然伊立替康（IRI）已被证明对多种癌症具有显著的疗效，但解决其相关的副作用仍然是临床关注的关键问题。化疗药物临床常与地塞米松（DEX）合用，以减少其副作用。此外，DEX可通过改善肿瘤微环境（tumor microenvironment， TME）和抗炎来增强抗肿瘤作用。因此，本研究构建IRI与DPD （DEX前药）共载脂质体（脂质体）以改善其毒副作用和抗肿瘤效果。脂质平均粒径为108.60 ± 0.36 nm，窄PDI为0.098 ± 0.020。进一步测定了IRI和DPD的包封效率（EE）均大于95 %。体外释放结果表明，脂质具有连续释放特性。细胞和动物实验表明，DPD的优先释放有助于改善TME，促进药物在肿瘤内的更大蓄积。此外，IRI与DPD联合应用也可以减少IRI引起的副作用，达到增效减毒的目的。因此，脂质具有良好的肿瘤抑制和临床应用前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Irinotecan and dexamethasone prodrug co-loaded liposomes for the treatment of breast cancer

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Irinotecan and dexamethasone prodrug co-loaded liposomes for the treatment of breast cancer

Cancer is a major global health challenge, which has a serious impact on human health and life. While Irinotecan (IRI) has been demonstrated to treat various cancers with remarkable efficacy, addressing its associated side effects remains a critical concern in clinical. Chemotherapy drugs are often used in combination with dexamethasone (DEX) in clinical practice to reduce their side effects. Besides, DEX can enhance the anti-tumor effect by improving tumor microenvironment (TME) and anti-inflammation. Therefore, in this study, IRI and DPD (DEX prodrug) co-loaded liposomes (LipID) were constructed to improve the side effects and anti-tumor efficacy. It was found that LipID had an average size of 108.60 ± 0.36 nm with a narrow PDI of 0.098 ± 0.020. The encapsulation efficiency (EE) of either IRI or DPD was further determined to be more than 95 %. Furthermore, the results of in vitro release indicated that LipID exhibited sequential release characteristics. Cells and animal experiments clarified that preferential release of DPD contributed to improving TME and facilitate greater accumulation of drugs within the tumors. Besides, the combined application of IRI and DPD could also reduce the side effects caused by IRI, achieving the goal of enhancing efficacy while minimizing toxicity. Therefore, LipID has excellent prospects for efficient tumor inhibition and clinical application.

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来源期刊

Journal of Controlled Release 医学-化学综合

CiteScore

18.50

自引率

5.60%

发文量

700

审稿时长

39 days

期刊介绍： The Journal of Controlled Release (JCR) proudly serves as the Official Journal of the Controlled Release Society and the Japan Society of Drug Delivery System. Dedicated to the broad field of delivery science and technology, JCR publishes high-quality research articles covering drug delivery systems and all facets of formulations. This includes the physicochemical and biological properties of drugs, design and characterization of dosage forms, release mechanisms, in vivo testing, and formulation research and development across pharmaceutical, diagnostic, agricultural, environmental, cosmetic, and food industries. Priority is given to manuscripts that contribute to the fundamental understanding of principles or demonstrate the advantages of novel technologies in terms of safety and efficacy over current clinical standards. JCR strives to be a leading platform for advancements in delivery science and technology.