Development, Optimization, and Characterization of Nanoengineered Drug Delivery Platforms for Tamoxifen: A Next-Generation Strategy for Sustained and Targeted Release in Hormone-Responsive Breast Cancer Treatment

Abstract

Tamoxifen, a selective estrogen receptor modulator, is widely used in the treatment of estrogen receptor-positive (ER+) breast cancer. However, its poor aqueous solubility and bioavailability limit its therapeutic effectiveness. This study aimed to develop Tamoxifen-loaded Nanoengineered Drug Delivery Platforms (NDDPs) to enhance its solubility, bioaccessibility, and cytotoxic potential. The formulations were optimized using solid and liquid lipids, surfactants, and stabilizers, ensuring high encapsulation efficiency (87–91%) and a controlled release profile. Particle size analysis showed that freshly prepared NDDPs were in the 41–43 nm range, while lyophilized formulations exhibited a slight increase in size (182–184 nm) but retained stability. In vitro drug release under simulated intestinal conditions followed a biphasic pattern, with sustained release up to 360 minutes (93.35–93.45%), supporting prolonged drug availability. Bioaccessibility studies demonstrated a 5-fold increase in micellar solubilization compared to pure Tamoxifen. Cytotoxicity evaluation using MCF-7 breast cancer cells revealed that NDDP-3 exhibited significantly enhanced cytotoxic effects compared to free Tamoxifen, reducing cell viability to 4.18% at lower concentrations. The results highlight the potential of lipid-based nanocarrier systems to enhance Tamoxifen’s therapeutic efficacy by improving drug delivery, bioavailability, and intracellular retention.