{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:16:10Z","timestamp":1788844570085,"version":"build-2803163510"},"reference-count":56,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Geneva"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats: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\u2013Burman 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\u00ae 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.<\/jats:p>","DOI":"10.3390\/pharmaceutics17040491","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T05:03:07Z","timestamp":1744174987000},"page":"491","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Liposomal Tubacin: Strategies for the Formulation of a Highly Hydrophobic Anticancer Drug"],"prefix":"10.3390","volume":"17","author":[{"given":"Cindy","family":"Schelker","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Faculty of Science, University of Geneva, 1211 Geneva, Switzerland"},{"name":"Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1211 Geneva, Switzerland"},{"name":"Translational Research Center in Oncohaematology, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9a","family":"Revaclier","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Faculty of Science, University of Geneva, 1211 Geneva, Switzerland"},{"name":"Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1211 Geneva, Switzerland"},{"name":"Translational Research Center in Oncohaematology, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6268-2586","authenticated-orcid":false,"given":"Gerrit","family":"Borchard","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Faculty of Science, University of Geneva, 1211 Geneva, Switzerland"},{"name":"Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1211 Geneva, Switzerland"},{"name":"Translational Research Center in Oncohaematology, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8299-0444","authenticated-orcid":false,"given":"Patrycja","family":"Nowak-Sliwinska","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Faculty of Science, University of Geneva, 1211 Geneva, Switzerland"},{"name":"Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1211 Geneva, Switzerland"},{"name":"Translational Research Center in Oncohaematology, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5747","DOI":"10.1038\/s41467-022-33375-w","article-title":"A transcriptional metastatic signature predicts survival in clear cell renal cell carcinoma","volume":"13","author":"Alchahin","year":"2022","journal-title":"Nat. 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