Engineering Red Blood Cell Membrane-Coated PLGA Nanoparticles for Kahweol Delivery: Formulation Development and Pharmacokinetic Assessment

Kahweol is an active diterpene with anti-inflammatory, antioxidant, and anticancer properties; however, its use may be limited by unfavorable pharmacokinetic characteristics. This study aimed to develop kahweol-loaded poly(lactic-co-glycolic acid) (PLGA) and red blood cell membrane-coated PLGA (RBC-PLGA) nanoparticles and evaluate their in vitro release behavior and in vivo pharmacokinetic profiles. Kahweol-loaded PLGA nanoparticles were prepared using the emulsification-solvent evaporation method and subsequently coated with rabbit erythrocyte membranes, a type of blood cell membrane, to obtain RBC-PLGA nanoparticles. Particle size, zeta potential, morphology, and encapsulation efficiency were characterized. In vitro release studies were performed using the dialysis bag method. Pharmacokinetic profiles of free kahweol, kahweol-loaded PLGA, and kahweol-loaded RBC-PLGA nanoparticles were evaluated in rabbits following intravenous administration (0.5 mg/kg), and plasma kahweol concentrations were analyzed by LC-MS/MS. PLGA and RBC-PLGA nanoparticles showed high encapsulation efficiency (>90%) and sustained biphasic release compared with the rapid burst release of free kahweol. Pharmacokinetic analysis demonstrated that PLGA and RBC-PLGA nanoparticles reduced peak plasma concentrations and prolonged systemic exposure. Among the nanoparticles, RBC-PLGA exhibited the most prolonged pharmacokinetic profile, with delayed time to maximum plasma concentration (Tmax), extended half-life, and increased overall exposure. The nanoparticles improved the pharmacokinetic profile of kahweol by enabling sustained release and prolonged systemic exposure, supporting their potential as delivery platforms for future applications.