Background: To reduce the nonspecifically distribution of chemotherapeutic agents throughout the whole
body, which causes severe toxicity in normal tissues, targeting them towards a receptor overexpressed on tumor
tissue, is a promising method for cancer therapy.
Objective: The aim of the present study was development of novel copolymeric micelles of raloxifene targeted
Styrene Maleic Acid-Poly Amide Ether Ester Imide-Poly Ethylene Glycol (SMA-PAEEI-PEG-RA) and loading them
with Docetaxel (DTX).
Methods: Successful synthesis of the targeted copolymer was confirmed by FTIR and C-NMR spectroscopy. The
micelles physicochemical properties like morphology, particle size, poly dispersity index, zeta potential, drug
loading, release, stability, in vitro cytotoxicity and cellular uptake were analyzed. The in vivo antitumor activity of
DTX-loaded micelles were assessed and compared with free DTX and non-targeted micelles in breast cancer bearing
Results: Particle sizes, zeta potentials and the encapsulation efficiency of the drug in targeted micelles were 115.9-
142.8 nm, -4.9 to -12.9 mV, and 54.1-67.8%, respectively. Cell toxicity tests showed that IC50 of DTX-loaded SMAPAEEI-
PEG-RA micelles increased five-fold as compared with free DTX. Survival rate of the mice improved more
effectively than free DTX so that, the percentage of increase in lifespan (ILS%) and the tumor inhibition ratio (TIR)
changed from 41.66% and 51.19% in free drug to 83.33% and 78.57% in the targeted micelles, respectively.
Conclusion: Therefore, the raloxifene conjugated PEG-derived micelles may provide a novel and effective delivery
system for DTX in breast cancer.