Folic acid grafted mixed polymeric micelles as a targeted delivery strategy for tamoxifen citrate in treatment of breast cancer.

Abstract The objective of this study was to develop folic acid (FA) grafted mixed polymeric micelles loaded with Tamoxifen citrate (TMXC) to enhance its antitumor activity in breast tissues. The conjugated FA-P123 micelles were prepared using carbonyl diimidazole cross-linker chemistry and confirmed using FTIR and 1HNMR. The micelles were examined for encapsulation efficiency, particle size, surface charge, in vitro release study, cytotoxic effect, and cellular uptake by a breast cancer cell line. The conjugated TMXC-loaded micelle exhibited a nanoparticle size of 35.01 ±1.20 nm, a surface charge of - 20.50 ± 0.95 mV, entrapped 87.83 ±5.10 % and released 67.58 ± 2.47 % of TMXC after 36 h. The conjugated micelles exhibited a significantly higher cellular uptake of TMXC by MCF-7 cell line and improved in vitro cytotoxicity by 2.48 folds compared to the TMXC-loaded unconjugated micelles. The results of in vivo studies indicated that TMXC-loaded FA-P123/P84 has a potential antitumor activity, as revealed by a significant reduction of tumor volume in tumor-bearing mice compared to TMXC-loaded unconjugated micelles. In conclusion, the obtained results suggested that conjugated FA-P123/P84 micelles could be an encouraging carrier for the treatment of breast cancer with TMXC.