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 folic acid Pluronic 123 (FA-P123) was prepared using carbonyl diimidazole cross-linker chemistry and confirmed using FTIR and 1HNMR. TMXC-loaded P123/P84 (unconjugated) and TMXC-loaded FA-P123/P84 (conjugated) micelles were examined for encapsulation efficiency, particle size, surface charge, in vitro drug release, 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 the 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.
Subject(s)
Micelles , Neoplasms , Mice , Animals , Tamoxifen , Folic Acid/chemistry , Poloxalene/chemistry , Cell Line, Tumor , Polymers/chemistry , Drug Carriers/chemistryABSTRACT
The main intent of this treatise was to encapsulate tamoxifen citrate (TMXC) into polymeric micellar delivery system and evaluate the influence of TMXC-loaded micelles as a promising carrier on the in vitro cytotoxicity and cellular uptake of TMXC in treatment of breast cancer. Different formulae of polymeric micelles loaded with TMXC using mixtures of different Pluronic polymers were fabricated by thin-film hydration method and evaluated for morphology, drug entrapment efficiency, particle size, surface charge, in vitro liberation of TMXC, uptake by cancer cell lines, and cytotoxic effect against breast cancer cell lines such as MCF-7. The optimal TMXC-loaded micelles exhibited nano-sized particles and entrapped about 89.09 ± 4.2% of TMXC. In vitro liberation study revealed an extended TMXC escape of about 70.23 ± 5.9% over a period of 36 h. The optimized TMXC-loaded micelles formula showed enhanced cellular uptake of TMXC by 2.28 folds and showed a significant cytotoxic effect with MCF-7 breast cancer cells compared to TMXC solution. The obtained yield proposed that Pluronic micelles could be a promising potential delivery system for anticancer moieties.
