Hydroxyurea-Loaded Nanostructured Lipid Carriers for Enhanced In Vitro Cytotoxicity and Drug Delivery

Hydroxyurea (HU) is an established anticancer drug used to treat chronic myelogenous leukemia, but its therapeutic efficacy is limited by rapid clearance, variable bioavailability, and dose-related toxicity. This study aimed to improve HU delivery by developing hydroxyurea-loaded nanostructured lipid carriers (NLCs) using different surfactant combinations. Three formulations, including NX-ST (Tween 80-SDS), NX-CT (Cremophor EL-Tween 80), and NX-CS (Cremophor EL-SDS), were prepared and evaluated for particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE), and cytotoxic activity. The formulations exhibited nanoscale particle sizes (67.377 to 110 nm), acceptable PDI (<0.35), high zeta potential (-30.033 to -46.433 mV), and good encapsulation efficiency (78.189 to 86.626%), indicating stable formulations. The release profile exhibited an approximately linear increase over the 0.5-6 h period, followed by a plateau. Cytotoxicity studies showed enhanced anticancer activity compared with free HU (IC₅₀ = 722.57 µg/mL). The formulation NX-ST demonstrated the highest cytotoxicity (IC₅₀ = 225 ± 21.47 µg/mL), consistent with enhanced drug delivery; the contribution of improved cellular uptake is inferred and was not directly measured in this study. The NLC formulations studied, particularly NX-ST, effectively enhanced HU's therapeutic performance by improving stability, delivery efficiency, and anticancer activity.