Therapeutic delivery · 2024
Cabozantinib-phospholipid complex for enhanced solubility, bioavailability, and reduced toxicity in liver cancer.
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Patil Jayesh, Bhattacharya Sankha, Saoji Suprit D, Dande Payal
Аннотация
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.
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.