Development, optimization, and characterization of docetaxel-loaded nanostructured lipid carriers for gastric cancer treatment

Gastric cancer remains a pressing health issue, with its global incidence projected to increase in the coming decades. Docetaxel, a widely used chemotherapeutic agent, is recommended for gastric cancer treatment, either as monotherapy or in combination with other drugs. However, its clinical performance is compromised by poor physicochemical properties, systemic and dose-limiting toxicities, drug resistance, and hypersensitivity reactions associated with marketed formulations. Integrating nanotechnology into drug delivery systems offers a forward-looking solution to these persistent challenges.

In this study, a rational design strategy was applied to develop and optimize nanostructured lipid carriers (NLC) for the localized delivery of docetaxel to gastric cancer cells. The resulting NLC dispersions were thoroughly characterized regarding colloidal stability, morphology, drug incorporation, in vitro release, drug-lipid interactions, thermal behavior, crystallinity, and cytotoxicity. Docetaxel-loaded NLC exhibited a uniform particle size (∼161 nm) and a zeta potential more negative than −20 mV, maintaining predefined quality standards over six months of storage at 4 °C and 25 °C. Approximately 98 % of docetaxel was incorporated, likely in an amorphous or molecularly dispersed state, within the semi-crystalline lipid matrix. A slow and sustained release profile was also obtained. Cell viability analysis at 48 h revealed that docetaxel-loaded NLC were more cytotoxic than the free drug at concentrations of 0.005 nM in AGS cells and 1 nM and 10 nM in NCI-N87 cells. The enhanced efficacy was driven by DTX entrapment, with no observed toxicity from the carrier. These findings suggest that the developed NLC could be a promising delivery system for improving docetaxel therapy in gastric cancer.