Background: Tamoxifen is widely used for the treatment of estrogen receptor-positive
breast cancer. However, it is associated with severe side effects of cancerous proliferation on the
uterus endometrium. The tumor-targeting formulation strategies can effectively overcome drug
side effects of tamoxifen and provide safer drug treatment.
Objective: This study aimed to design tumor-targeted PLGA nanoparticles of tamoxifen by attaching
hyaluronic acid (HA) as a ligand to actively target the CD44 receptors present at breast cancer
Methods: PLGA-PEG-HA conjugate was synthesized in the laboratory, and its tamoxifen-loaded
nanoparticles were fabricated and characterized by FTIR, NMR, DSC, and XRD analysis. Formulation
optimization was done by Box-Behnken design using Design-Expert software. The formulations
were evaluated for in vitro drug release and cytotoxic effect on MCF-7 cell lines.
Results: The particle size, PDI, and drug encapsulation efficiency of optimized nanoparticles were
294.8, 0.626, and 65.16%, respectively. Optimized formulation showed 9.56% burst release and
sustained drug release for 8h. The drug release was affected by non-Fickian diffusion process and
supplemented further by the erosion of polymeric matrix which followed the Korsmeyer-Peppas
model. MTT cell line assay showed 47.48% cell mortality when treated with tamoxifen-loaded PLGA-
Conclusion: Hyaluronic acid conjugated PLGA-PEG nanoparticles of tamoxifen were designed for
active targeting to cancerous breast cells. The results of the MTT assay showed that tamoxifen
nanoparticles formulation was more cytotoxic than tamoxifen drug alone, which is attributed to
their preferential uptake by cell lines by the affinity of CD44 receptors of cell lines to HA ligand
present in nanoparticles.