Patil Jayesh, Bhattacharya Sankha, Saoji Suprit D, Dande Payal
Department of Pharmaceutics, School of Pharmacy & Technology Management, SVKM'S NMIMS Deemed-to-be University, Shirpur, India.
Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University Nagpur, Mahatma Jyotiba Fuley Shaikshanik Parisar, University Campus, Nagpur, India.
Ther Deliv. 2025 Jan;16(1):25-41. doi: 10.1080/20415990.2024.2435240. Epub 2024 Nov 29.
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.
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.
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.
通过开发卡博替尼-磷脂复合物（CBZ-PLS）来提高卡博替尼（CBZ）的治疗潜力，CBZ是一种酪氨酸激酶抑制剂，具有水溶性有限、生物利用度低和毒性高的特点。
采用溶剂蒸发法结合Box-Behnken设计制备CBZ-PLS，并使用各种技术对其进行表征以确认分子间相互作用。评估了溶解度、体外释放、药代动力学和毒性。还评估了对HepG2细胞系的细胞毒性作用。
CBZ-PLS的溶解度增加了126倍，并增强了CBZ的体外释放。对Wistar大鼠的药代动力学研究表明生物利用度提高了1.58倍，而急性毒性研究证实了其生物相容性。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、增加活性氧生成和更高的DNA片段化。该复合物在6个月内也保持稳定。
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，为更有效的肝癌治疗提供了一种有前景的方法。
