Posted by Paclitaxel (PCTX) is one of the most prevalently used chemotherapeutic agents. However, its use is currently beset with a host of problems: solubility issue, microplastic leaching, and drug resistance. In this study, the aqueous solubility of sugars was harnessed, and the high affinity of cancer cells for them, to entrap the hydrophobic PCTX within the hydrophilic shell of β-cyclodextrin. This novel drug formulation was characterized by testing its various physical and chemical parameters. Importantly, in all in vitro assays, the conjugate performed better than the drug alone. It was found that the conjugate is internalized by the cancer cells (A549) via caveolin 1-mediated endocytosis. Thereafter, it triggers apoptosis by inducing the formation of reactive oxygen species. Based on experiments on zebrafish larvae, the formulation displays lower toxicity compared to PCTX alone. Thus, this “Trojan Horse” approach, relying on minimal components and relatively faster formulation, enhances the anti-tumor potential of PCTX, while simultaneously making it more innocuous toward non-cancerous cells.
Sautan Show, Debanjan Dutta, Upendra Nongthomba, Mahadesh Prasad A J, Effective paclitaxel: β-Cyclodextrin-based formulation boosts in vitro anti-tumor potential and lowers toxicity in zebrafish. Toxicology Research 13, October 2024, tfae150, https://doi.org/10.1093/toxres/tfae150