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Published on: February 9, 2019
Cabozantinib-phospholipid complex for enhanced solubility, bioavailability, and reduced toxicity in liver cancer
Jayesh Patil1, Sankha Bhattacharya1, Suprit D Saoji2
1Department of Pharmaceutics, School of Pharmacy & Technology Management, SVKM'S NMIMS Deemed-to-be University, Shirpur, India.
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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