PEGylated liposomes enhance the pharmacokinetics, biodistribution, anticancer efficacy, and safety of Kaempferol, a phytomolecule enrolled in clinical trials
摘要
Kaempferol, a phytomolecule currently in Phase I clinical trials, is also being explored for its nutraceutical potential. However, its clinical utility is limited due to poor bioavailability. Previous studies suggest that intravenous administration of PEGylated liposomes can markedly improve the pharmacokinetic profile and systemic availability of phytochemicals, while enabling controlled release through the enhanced permeability and retention (EPR) effect. In the present study, we prepared and validated polyethylene glycol (PEG) modified Kaempferol liposome which possess a particle size, polydispersity index (PDI) and zeta potential of 136.60 ± 0.37 nm, 0.1540 ± 0.020 and -37.0 ± 8.19 mV respectively. PEG-LP-KP exhibited an entrapment efficiency of ~ 92% and shows a sustained Kaempferol release upon 24 h at pH 5.5. Our study indicates that intravenous administration of PEG-LP-KP significantly improves the pharmacokinetic parameters such as AUC(0-24), Cmax and Vd compared with pure Kaempferol at three different doses (10 mg/kg, 20 mg/kg & 30 mg/kg). The biodistribution study indicated that Kaempferol encapsulated into the liposome shows a high accumulation in the