2. Academic Validation
  3. Enhancement of the in vitro anti-leukemic effect of the histone deacetylase inhibitor romidepsin using Poly-(D, L-lactide-co-glycolide) nanoparticles as a drug carrier

Enhancement of the in vitro anti-leukemic effect of the histone deacetylase inhibitor romidepsin using Poly-(D, L-lactide-co-glycolide) nanoparticles as a drug carrier

  • Eur J Pharm Sci. 2025 Feb 12:207:107043. doi: 10.1016/j.ejps.2025.107043.
Pinyadapat Aroonthongsawat 1,  Siriphan Manocheewa 2,  Chatchawan Srisawat 3,  Primana Punnakitikashem 4,  Yaneenart Suwanwong 5
Affiliations

Affiliations

  • 1 Department of Clinical Microscopy, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
  • 2 Siriraj Metabolomics and Phenomics Center, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
  • 3 Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Bangkok 10700, Thailand; Siriraj Center of Research Excellence in Theranostic Nanomedicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
  • 4 Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Bangkok 10700, Thailand; Siriraj Center of Research Excellence in Theranostic Nanomedicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. Electronic address: primana.pun@mahidol.ac.th.
  • 5 Department of Clinical Microscopy, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand; Center of Excellence for Biosensors and Bioengineering (CEBB), Chulalongkorn University, Bangkok, 10330, Thailand. Electronic address: yaneenart.s@chula.ac.th.
PMID: 39952370 DOI: 10.1016/j.ejps.2025.107043
Abstract

The goal of this work is to develop a delivery system for histone deacetylase inhibitor (HDACi) romidepsin (ROM) using Poly(D, L-lactide-co-glycolide) as a carrier and evaluate its anti-leukemic effects. Romidepsin-loaded nanoparticles (ROM NPs) required for this purpose were fabricated using a single emulsion-solvent evaporation technique. Their physical characteristics and in vitro drug release profiles were studied, alongside biocompatibility and hemocompatibility assessments. Cell viability assays and Annexin V/Propidium Iodide (PI) staining were conducted to evaluate the anti-leukemic and Apoptosis induction efficiency of ROM NPs in vitro. ROM NPs displayed a spherical shape with an average hydrodynamic size of about 149.7 ± 8.4 nm, a PDI of 0.11 ± 0.03, and a zeta potential of -25.27 ± 2.12 mV. The nanoparticles demonstrated a high encapsulation efficiency of ROM (∼93 %) and these nanoparticles effectively entered acute leukemia cells, including U937 and Jurkat. ROM NPs also exhibited a prolonged biphasic release pattern, specifically, the initial burst release phase occurred within the first 24 h, followed by a slower, sustained release. Additionally, they showed no hematological or biological toxicity, indicating their potential use for the delivery of anti-cancer drugs through the circulatory system. In tests on acute leukemia cell lines, ROM NPs showed significantly stronger anti-leukemic effects and induced Apoptosis to a greater extent compared to free ROM. In summary, ROM NPs represent a promising therapy option for leukemia according to their enhanced anti-leukemic effects. Further modification of this strategy could be performed to enable target specificity, hence minimizing damage to normal cells.

Keywords

Leukemia; Nano-delivery; Poly(D, L-lactide-co-glycolide); Romidepsin.

Figures
Products