Cabozantinib-phospholipid complex for enhanced solubility, bioavailability, and reduced toxicity in liver cancer.

IF 3 Q2 PHARMACOLOGY & PHARMACY

Therapeutic delivery Pub Date : 2025-01-01 Epub Date: 2024-11-29 DOI:10.1080/20415990.2024.2435240

Jayesh Patil, Sankha Bhattacharya, Suprit D Saoji, Payal Dande

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引用次数: 0

Abstract

Aims: To enhance the therapeutic potential of Cabozantinib (CBZ), a tyrosine kinase inhibitor with limited water solubility, low bioavailability, and high toxicity, by developing a Cabozantinib-Phospholipid Complex (CBZ-PLS).

Materials & methods: CBZ-PLS was formulated using solvent evaporation with a Box-Behnken design and characterized using various techniques to confirm molecular interactions. Solubility, in vitro release, pharmacokinetics, and toxicity were evaluated. Cytotoxic effects on HepG2 cell lines were also assessed.

Results: CBZ-PLS exhibited a 126-fold increase in solubility and enhanced CBZ release in vitro. Pharmacokinetic studies on Wistar rats demonstrated a 1.58-fold increase in bioavailability, while acute toxicity studies confirmed biocompatibility. CBZ-PLS showed superior cytotoxicity, apoptosis induction, migration inhibition, increased ROS generation, and greater DNA fragmentation in HepG2 cells. The complex also maintained stability over 6 months.

Conclusions: CBZ-PLS significantly improves the solubility, bioavailability, and therapeutic efficacy of CBZ against liver cancer, presenting a promising approach for more effective liver cancer treatment.

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卡博赞替尼-磷脂复合物增强溶解度，生物利用度，降低肝癌毒性。

目的：通过开发Cabozantinib-磷脂复合物（CBZ- pls），提高Cabozantinib （CBZ）的治疗潜力，Cabozantinib是一种水溶性有限、生物利用度低、毒性高的酪氨酸激酶抑制剂。材料与方法：采用Box-Behnken设计的溶剂蒸发方法配制CBZ-PLS，并使用各种技术确定分子相互作用。对其溶解度、体外释放、药代动力学和毒性进行了评价。对HepG2细胞系的细胞毒作用也进行了评估。结果：CBZ- pls的溶解度提高了126倍，体外释放CBZ增强。Wistar大鼠的药代动力学研究表明，生物利用度增加1.58倍，而急性毒性研究证实了生物相容性。CBZ-PLS在HepG2细胞中表现出优异的细胞毒性、诱导凋亡、抑制迁移、增加ROS生成和更大的DNA片段化。该综合体也保持了6个多月的稳定。结论：CBZ- pls显著提高了CBZ对肝癌的溶解度、生物利用度和治疗效果，为更有效地治疗肝癌提供了一条有希望的途径。

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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来源期刊

Therapeutic delivery PHARMACOLOGY & PHARMACY-

CiteScore

5.50

自引率

0.00%

发文量

期刊介绍： Delivering therapeutics in a way that is right for the patient - safe, painless, reliable, targeted, efficient and cost effective - is the fundamental aim of scientists working in this area. Correspondingly, this evolving field has already yielded a diversity of delivery methods, including injectors, controlled release formulations, drug eluting implants and transdermal patches. Rapid technological advances and the desire to improve the efficacy and safety profile of existing medications by specific targeting to the site of action, combined with the drive to improve patient compliance, continue to fuel rapid research progress. Furthermore, the emergence of cell-based therapeutics and biopharmaceuticals such as proteins, peptides and nucleotides presents scientists with new and exciting challenges for the application of therapeutic delivery science and technology. Successful delivery strategies increasingly rely upon collaboration across a diversity of fields, including biology, chemistry, pharmacology, nanotechnology, physiology, materials science and engineering. Therapeutic Delivery recognizes the importance of this diverse research platform and encourages the publication of articles that reflect the highly interdisciplinary nature of the field. In a highly competitive industry, Therapeutic Delivery provides the busy researcher with a forum for the rapid publication of original research and critical reviews of all the latest relevant and significant developments, and focuses on how the technological, pharmacological, clinical and physiological aspects come together to successfully deliver modern therapeutics to patients. The journal delivers this essential information in concise, at-a-glance article formats that are readily accessible to the full spectrum of therapeutic delivery researchers.