Background:
Due to the low water solubility of Docetaxel (DTX), it is formulated with
ethanol and Tween 80 with lots of side effects. For this reason, special attention has been paid to formulate
it in new drug nano-carriers.
Objective:
The goal of this study was to evaluate the safety, antitumor activity and tissue distribution
of the novel synthesized Raloxifene (RA) targeted polymeric micelles.
Methods:
DTX-loaded RA-targeted polymeric micelles composed of poly(styrene-maleic acid)-
poly(amide-ether-ester-imide)-poly(ethylene glycol) (SMA-PAEE-PEG) were prepared and their antitumor
activity was studied in MC4-L2 tumor-bearing mice compared with non-targeted micelles and
free DTX. Safety of the micelles was studied by Hematoxylin and Eosin (H&E) staining of tumors and
major organs of the mice. The drug accumulation in the tumor and major organs was measured by
HPLC method.
Results:
The results showed better tumor growth inhibition and increased survival of mice treated with
DTX-loaded in targeted micelles compared to the non-targeted micelles and free DTX. Histopathological
studies, H&E staining of tumors and immunohistochemical examination showed the potential
of DTX-loaded RA-targeted micelles to inhibit tumor cells proliferation. The higher accumulation
of the DTX in the tumor tissue after injection of the micelles compared to the free DTX may indicate
the higher uptake of the targeted micelles by the G-Protein-Coupled Estrogen Receptors (GPER).
Conclusion:
The results indicate that RA-conjugated polymeric micelles may be a strong and effective
drug delivery system for DTX therapy and uptake of the drug into tumor cells, and overcome the disadvantages
and side effects of conventional DTX.
