The Integration of Cholesterol‐Polyethylene Glycol‐Folic Acid Conjugate and Iron Oxide Nanoparticles for A Multi Targeted and Stimuli Responsive Drug Delivery System of Quercetin

ABSTRACT This research focused on developing a multi‐targeted, stimuli‐responsive drug delivery system by integration of iron oxide nanoparticles (IONPs) and Cholesterol‐Polyethylene glycol‐Folic acid conjugate (CPF) to enhance the delivery of poorly water‐soluble drugs. Oleic acid (OA) coated iron oxide nanoparticles (OCION) were synthesized and subsequently functionalized with CPF to form OCION–CPF. Quercetin (QCT), a model poorly soluble drug, was encapsulated into the system using the thin film method. Analytical techniques, including dynamic light scattering (DLS), zeta potential measurement, Fourier‐transform infrared spectroscopy (FT‐IR), proton nuclear magnetic resonance ( 1 H‐NMR) and energy‐dispersive X‐ray spectroscopy (EDX), confirmed the successful synthesis and functionalization of the nanoparticles. The OCION–CPF system demonstrated high encapsulation efficiency for QCT and pH‐responsive drug release, as shown by loading capacity and release kinetics study. The system exhibited dual‐targeting potential due to the magnetic properties of OCION and the folate receptor binding ability conferred by folic acid (FA) modification. The integration of OA, Chol, PEG, and FA into IONPs addressed the limitations of individual targeting strategies, enhancing the stability and effectiveness of the nanoparticles for delivering poorly water‐soluble drugs. This approach presents a promising advancement in targeted and efficient drug delivery technologies.