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

Article Article scientifique Article Liposomal Tubacin: Strategies for the Formulation of a Highly Hydrophobic Anticancer Drug eng 2025-04-08 author Schelker Cindy 771886 Section des sciences pharmaceutiques (FARMA) author Revaclier Léa Manon 875472 author Borchard Gerrit 0000-0001-6268-2586 635281 Section des sciences pharmaceutiques (FARMA) author Nowak-Sliwinska Patrycja 0000-0002-8299-0444 848409 Section des sciences pharmaceutiques (FARMA) 491 10.3390/pharmaceutics17040491 1999-4923 https://www.mdpi.com/1999-4923/17/4/491 <p>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.</p> The data supporting this work are accessible at: Schelker, Cindy; Revaclier, Léa; Borchard, Gerrit; Nowak-Sliwinska, Patrycja (2025), “Tubacin encapsulation”, Mendeley Data, V2, doi: 10.17632/zgcgvkv42d.2. Design of experiment Drug delivery Histone deacetylase inhibitors Liposomes Plackett–Burmann Tocopheryl polyethylene glycol succinate Dewey 615 31 Section des sciences pharmaceutiques 17 false 1325 Pharmacologie moléculaire Pharmaceutics 17 4 caed9018-5260-4609-b36f-77edea825ada Article (Accepted version) Public pharmaceutics-17-00491.pdf 1609483 application/pdf CC BY-4.0 a3e8821fe8def0d22570a063b45a115433ebdb5cb3a9e5c5b9432671173f2bc8 Vignette Public pharmaceutics-17-00491-ag.png 87414 image/png openAccess Faculté des sciences / Section des sciences pharmaceutiques

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Liposomal Tubacin: Strategies for the Formulation of a Highly Hydrophobic Anticancer Drug	Pharmaceutics			2025	42	327

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Revaclier, Léa Manon