Development of venetoclax with 2-hydroxypropyl-beta-cyclodextrin inclusion complex for improved bioavailability

Abstract

Cyclodextrin complexes loaded with venetoclax for improved solubility and therapeutic efficacy as repurposed drug. The venetoclax-cyclodextrin inclusion complex was prepared using kneading method. Primarily in-silico molecular docking study was performed to examine the possible interaction between venetoclax and hydroxypropyl-β-cyclodextrin (HP-β-CD) and extensively characterized. The in-vitro studies were performed using A-549 lung epithelial cancer cells. The in-vivo pharmaco-kinetic studies was performed on wistar rats. The aqueous solubility of venetoclax was increased upto 3.16 folds, as compared with pure venetoclax with entrapment efficiency (EE%) was determined 95.44 ± 0.3%. In-vitro cytotoxicity studies were carried on A-549 lung epithelial cancer cells, wherein BCL-2 receptors were highly over-expressed and IC 50 values for venetoclax and venetoclax- HP-β-CD complex was calculated at 24 and 48 hrs in the order of 1.241 µg/ml, 0.68 µg/ml and 0.757719 µg/ml, 0.6125 µg/mL, respectively. The oral bioavailability was increased 4.03 times compared to the pure drug. The venetoclax-HP-β-CD inclusion complexes showed the increased aqueous solubility with improved anticancer activities.

Communicated by Ramaswamy H. Sarma

Keywords:

• Cyclodextrin
• lung epithelial
• molecular modeling
• caspase
• MTT assay

Acknowledgements

We acknowledge toe the Department of Pharmaceuticals, National Institute of Pharmaceutical Education and Research NIPER Hyderabad, Ministry of Chemicals and Fertilizers, New Delhi.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors reported there is no funding associated with the work featured in this article.