# Liposomal Tubacin: Strategies for the Formulation of a Highly Hydrophobic Anticancer Drug

## TL;DR

This paper explores using liposomes to improve the delivery of tubacin, a hydrophobic anticancer drug, to make it more effective and less toxic for treating kidney cancer.

## Contribution

The study introduces a novel liposomal formulation strategy to enhance the delivery and reduce toxicity of hydrophobic anticancer drugs like tubacin.

## Key findings

- Initial liposomal formulations reduced mitochondrial activity to 30% in healthy renal cells.
- Optimized formulations preserved up to 80% mitochondrial activity in noncancerous cells while maintaining therapeutic properties.
- Liposomal encapsulation improves the safety and delivery of hydrophobic drugs like tubacin for cancer treatment.

## Abstract

Background: Clear-cell renal cell carcinoma (ccRCC) is the most prevalent form of kidney cancer, accounting for over 75% of cases worldwide. Histone deacetylase inhibitors (HDACIs) have emerged as promising agents for ccRCC treatment, particularly in combination with immunotherapy or targeted therapies. Tubacin, a potent HDAC6 inhibitor, has demonstrated potent anticancer activity but faces therapeutic limitations due to its hydrophobic nature and poor solubility, which hinder its effective drug delivery. This study explores liposomal encapsulation as a strategy to improve tubacin delivery; Methods: Liposomes were prepared using the ethanol injection method followed by size-exclusion chromatography. Using the Plackett–Burman Design, we identified a promising liposomal formulation and evaluated its biological activity in vitro; Results: However, initial formulations reduced the mitochondrial activity to 30% in healthy renal cell lines. To mitigate this, we optimized the formulation by reducing tocopheryl polyethylene glycol succinate (TPGS) content and incorporating Kolliphor® as an additional surfactant. This optimized formulation significantly reduced toxicity in noncancerous cells, with up to 80% of mitochondrial activity conserved while retaining key properties for therapeutic application; Conclusions: Our findings demonstrate that liposomal encapsulation enhances the safety and delivery of hydrophobic drugs like tubacin. This approach offers a promising strategy for improving the efficacy of HDACIs in ccRCC treatment, potentially overcoming drug delivery challenges associated with hydrophobic molecules.