Prolonging the Half-Life of Histone Deacetylase Inhibitor Belinostat via 50 nm Scale Liposomal Subcutaneous Delivery System for Peripheral T-Cell Lymphoma

Abstract

Lymph node metastasis is an aggressive condition characterized by poor treatment outcomes and low overall survival. Belinostat is a novel histone deacetylase (HDAC) inhibitor approved by the Food and Drug Administration (FDA) for the treatment of relapsed peripheral T-cell lymphoma (PTCL). However, the major problem is that belinostat has a short half-life of 1.1 h. In this study, we successfully prepared 50 nm liposomal colloids, which showed a controlled release pattern and excellent pharmacokinetics. The results showed that the particle size of liposomes consisting of dioleoylphosphatidylcholine (DOPC) was larger than that of those consisting of dioleoylglycerophosphoserine (DOPS). In terms of release kinetics of belinostat, the free drug was rapidly released and showed lower area under curve (AUC) exposure for in vivo pharmacokinetics. When liposomal formulations were employed, the release pattern was fitted with Hixson–Crowell models and showed sustained release of belinostat. Moreover, HuT-78 cells were able to take up all the liposomes in a concentration-dependent manner. The safety assessment confirmed hemocompatibility, and the platelet count was increased. Furthermore, the liposomes consisting of DOPC or DOPS had different behavior patterns, and their delivery to lymphatic regions should be thoroughly investigated in the future.

Liposome cocktail activator modulates hepatocytes and remodels the microenvironment to mitigate acute liver failure

“…The cellular uptake of C-activator by LO2 cells were determined using flow cytometry. Rhodamine B (RhB) was used as a fluorescence indicator to replace dimethyl itaconate and Rhodamine B-loaded liposomes (RhB-Lip) were prepared using the same method as mentioned above to assess liposomal intracellular uptake [29] . Briefly, LO2 cells were seeded in 12-well plates and then incubated at 37 °C until 60%−80% confluence was reached.…”

Update on histone deacetylase inhibitors in peripheral T-cell lymphoma (PTCL)

“…Synergistic effects between belinostat and proteasome inhibitor ixazomib [ 88 ] or dihydrofolate reductase inhibitor pralatrexate [ 89 ] have been demonstrated in T-cell lymphoma (TCL) in vitro, providing clues for combination drug trials. In addition, a scale liposomal subcutaneous delivery system of belinostat has been successfully designed for PTCLs to prolong the short half-life of 1.1 h and improve the burst effect and pharmacokinetic properties [ 90 ]. However, this novel system temporarily lacks test data in the human body.…”