Tamoxifen loaded lipid nanoparticles as a novel therapeutic approach enhancing apoptotic cell death in triple negative breast cancer cells

Tamoxifen (TMX), a selective estrogen receptor modulator, is widely used to treat hormone-dependent breast cancer (BC). Nevertheless, low bioavailability, and emerging deleterious effects considerably restrict TMX clinical application. This study aimed to develop and comprehensively characterize TMX-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), to comparatively assess their physicochemical performance and to evaluate their therapeutic potential against triple-negative BC (TNBC). After production, those lipid nanoparticles (LNPs) were characterized in terms of particle size, polydispersity index, zeta potential, morphological investigation through transmission electron microscopy analysis, identifications of interactions via FT-IR and differential scanning calorimetry, entrapment efficiency, drug loading, drug release study, long-term stability for 7 months, cell viability and flow cytometry analysis to evaluate antitumor efficacy of drug carriers. TMX loaded LNPs (15 mg) were produced with small size (< 200 nm), homogeneous dispersion (< 0.3) and high entrapment efficiency (> 90%). FT-IR spectra and differential scanning calorimetry profiles confirmed TMX conjugation into LNPs. TMX showed higher release from NLCs, whereas SLNs showed retarded release. Particle concentration was reduced 10-30 times after TMX loading. Moreover, TMX-loaded LNPs effectively inhibited cell viability on TNBC (MDA-MB-231), mainly based on apoptosis. These findings suggest that TMX-loaded LNPs represent a promising preclinical strategy for enhancing TMX efficacy against TNBC cells.