Improving the Thrombocytopenia Adverse Reaction of Belinostat Using Human Serum Albumin Nanoparticles.
Humans
Sulfonamides
/ pharmacokinetics
Hydroxamic Acids
/ chemistry
Nanoparticles
/ chemistry
Thrombocytopenia
/ chemically induced
Molecular Docking Simulation
Histone Deacetylase Inhibitors
/ pharmacokinetics
Serum Albumin, Human
/ chemistry
Animals
Particle Size
Male
Cell Line, Tumor
Cell Survival
/ drug effects
Drug Carriers
/ chemistry
Solubility
belinostat
human serum albumin nanoparticles
peripheral T-cell lymphoma
pharmacokinetics
thrombocytopenia
Journal
International journal of nanomedicine
ISSN: 1178-2013
Titre abrégé: Int J Nanomedicine
Pays: New Zealand
ID NLM: 101263847
Informations de publication
Date de publication:
2024
2024
Historique:
received:
02
05
2024
accepted:
17
10
2024
medline:
30
10
2024
pubmed:
30
10
2024
entrez:
30
10
2024
Statut:
epublish
Résumé
Belinostat, a histone deacetylase inhibitor used for hematological cancer treatments, however, it caused thrombocytopenia, poor solubility, and rapid clearance. To mitigate these issues, human serum albumin (HSA) was utilized as the core material for its high protein binding affinity and self-binding capabilities. The study focused on developing belinostat-loaded HSA nanoparticles to improve solubility, extend circulation time, and reduce adverse effects. Belinostat-loaded HSA nanoparticles were synthesized using a desolvation method, optimized for size, charge, and entrapment efficiency, and characterized by molecular docking and Fourier-transform infrared spectroscopy (FTIR). Cytotoxicity was assessed in vitro against HuT-78 cells, and in vivo pharmacokinetics and toxicology studies were conducted to evaluate therapeutic efficacy and safety. The prepared belinostat-HSA nanoparticles exhibited the size of 150 nm with a charge of ~-50 mV and a high entrapment efficiency (90%). Molecular docking confirmed that belinostat and HSA had a strong binding affinity (-9.5 kcal mol In conclusion, the belinostat-loaded HSA nanoparticles significantly enhance the solubility and half-life of belinostat, reduce its adverse hematological effects, and maintain sustained drug release. These attributes underscore the potential of belinostat-HSA nanoparticles as a viable intravenous option for the treatment of hematological malignancies.
Sections du résumé
Background
UNASSIGNED
Belinostat, a histone deacetylase inhibitor used for hematological cancer treatments, however, it caused thrombocytopenia, poor solubility, and rapid clearance. To mitigate these issues, human serum albumin (HSA) was utilized as the core material for its high protein binding affinity and self-binding capabilities. The study focused on developing belinostat-loaded HSA nanoparticles to improve solubility, extend circulation time, and reduce adverse effects.
Methods
UNASSIGNED
Belinostat-loaded HSA nanoparticles were synthesized using a desolvation method, optimized for size, charge, and entrapment efficiency, and characterized by molecular docking and Fourier-transform infrared spectroscopy (FTIR). Cytotoxicity was assessed in vitro against HuT-78 cells, and in vivo pharmacokinetics and toxicology studies were conducted to evaluate therapeutic efficacy and safety.
Results
UNASSIGNED
The prepared belinostat-HSA nanoparticles exhibited the size of 150 nm with a charge of ~-50 mV and a high entrapment efficiency (90%). Molecular docking confirmed that belinostat and HSA had a strong binding affinity (-9.5 kcal mol
Conclusion
UNASSIGNED
In conclusion, the belinostat-loaded HSA nanoparticles significantly enhance the solubility and half-life of belinostat, reduce its adverse hematological effects, and maintain sustained drug release. These attributes underscore the potential of belinostat-HSA nanoparticles as a viable intravenous option for the treatment of hematological malignancies.
Identifiants
pubmed: 39474124
doi: 10.2147/IJN.S475823
pii: 475823
pmc: PMC11520922
doi:
Substances chimiques
Sulfonamides
0
Hydroxamic Acids
0
belinostat
F4H96P17NZ
Histone Deacetylase Inhibitors
0
Serum Albumin, Human
ZIF514RVZR
Drug Carriers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
10785-10800Informations de copyright
© 2024 Liu et al.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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