Formulation and Characterization of TPGS-Coated Cabazitaxel Liposomes: In-Vitro Cytotoxicity, Drug Release, and In-Silico Metabolic Modulation

Abstract

Purpose

Cabazitaxel (CBZ) is a semi-synthetic anti-cancer drug and belongs to BCS class IV category with poor water solubility and low permeability. Its clinical effectiveness is further limited by extensive metabolism mediated by CYP3A4 and CYP2C8 enzymes. Liposome-based drug delivery systems offer a promising strategy to overcome these limitations by enhancing aqueous solubility and bioavailability, while potentially reducing CYP-mediated metabolism. However, recent studies suggest that CBZ may have therapeutic potential for breast cancer.

Method

The present study aimed to develop CBZ-loaded drug delivery and enhance cytotoxicity in MCF-7 (breast cancer cells) using TPGS coated liposomes. TPGS-CBZ-Liposomes were prepared by the thin-film hydration method followed by probe ultrasonication.

Results

TPGS-CBZ-liposome demonstrated mean particle sizes of 146.8 ± 3.09 nm (PDI 0.035 ± 0.008) and (zeta potential − 3.70 ± 0.68 mV). Compared with pure CBZ, TPGS-CBZ-liposomes showed improved stability and achieved encapsulation efficiency greater than 98% with 2.27% drug loading. TEM analysis confirmed TPGS coating on the liposomal surface. The TPGS-coated liposomes enhanced CBZ solubility and provided sustained drug release for up to 72 hrs. P-XRD and DSC analyses showed that CBZ was present in an amorphous form within the formulation. Moreover, cell viability studies revealed significantly higher cytotoxicity of TPGS-CBZ liposomes compared with pure CBZ solution.

Conclusion

TPGS can be considered a key modifier for enhancing multiple quality attributes of liposomal formulations, including bioavailability, solubility, controlled release profile, and cytotoxicity. These findings highlight the potential of TPGS-coated liposomes as an effective platform for anticancer drug, thereby potentially expanding its clinical applications. A thorough in-silico evaluation identified Capsaicin (CAP) and Dihydrocapsaicin (DHC) as promising inhibitors of CBZ metabolism via CYP3A4 and CYP2C8 enzymes.

Future Research

Considering these outcomes, the formulations warrant further preclinical evaluation in suitable animal models to assess therapeutic efficacy. Additionally, the CBZ–CAP combination may significantly affect the pharmacokinetic and pharmacodynamic profiles of CBZ.

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Dhole, D., Jat, S., Prabakaran, A. et al. Formulation and Characterization of TPGS-Coated Cabazitaxel Liposomes: In-Vitro Cytotoxicity, Drug Release, and In-Silico Metabolic Modulation. J Pharm Innov 21, 466 (2026). https://doi.org/10.1007/s12247-026-10665-0

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