Synthesis And In Vitro/In Vivo Characterization Of Raloxifene Grafted Poly(Styrene Maleic Acid)-Poly (Amide-Ether-Ester-Imide¬¬) Micelles For Targeted Delivery Of Docetaxel In G Protein-Coupled Estrogen Receptor Breast Cancer.

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 Balb-c mice.

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 SMA-PAEEI-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.