Docetaxel-conjugated bile acid-derived nanomicelles can inhibit tumour progression with reduced toxicity†

Docetaxel (DTX) is a highly effective chemotherapy drug commonly employed in the management of multiple cancers, such as breast, lung, and prostate cancer. However, its clinical usage is significantly hampered by its limited solubility, which limits its bioavailability, and its considerable toxic effects like neutropenia, neuropathy, and hypersensitive reactions. These limitations necessitate the development of innovative formulations to boost the therapeutic index of DTX. In this study, we aimed to enhance the tolerability and reduce the toxic effects of DTX by developing a novel hybrid scaffold (PIP-LCA-DTX), where we conjugated DTX to piperidine-derived lithocholic acid. This hybrid scaffold integrates the beneficial properties of bile acid-based drug conjugates and cationic amphiphiles to form stable and effective drug delivery systems. Our research demonstrates that PIP-LCA-DTX exhibits similar anticancer properties to DTX when tested against murine colon cancer (CT26) and melanoma (B16-F10) cell lines, indicating that the hybrid retains the therapeutic efficacy of the original drug. Our findings revealed that PIP-LCA-DTX forms stable nanomicelles (DTX-NMs) with an average hydrodynamic diameter of <150 nm and provides a promising delivery system by enhancing the solubility and stability of DTX. DTX-NMs showed significantly better tolerability and enhanced therapeutic efficacy (survival) compared to DTX alone. This improved tolerability, combined with the maintained therapeutic efficacy of DTX-NMs against murine cancer models, suggests that this hybrid scaffold could offer a more viable and safer option for cancer treatment.