The aim of present study was to develop conventional and PEGylated (long circulating),
liposomes containing
anastrozole (ANS) for effective treatment of
breast cancer. ANS is a third-generation non-steroidal
aromatase inhibitor of the
triazole class used for the treatment of advanced and late-stage
breast cancer in post-menopausal women. Under such disease conditions the median
duration of therapy should be prolonged until
tumor regression ends (>31 months).
Liposomes were prepared by the thin film hydration method by using ANS and various
lipids such as soyaphosphatidyl
choline,
cholesterol and methoxy
polyethylene glycol distearoyl
ethanolamine in different concentration ratios and evaluated for physical characteristics, in vitro drug release and stability. Optimized formulations of
liposome were studied for in vitro cytotoxic activity against the BT-549 and MCF-7 cell lines and in vivo behavior in Wistar rats. Preformulation studies, both Fourier transform infrared study and differential scanning calorimetry analysis showed no interaction between the
drug and the
excipients used in the formulations. The optimized formulations AL-07 and AL-09
liposomes showed encapsulation efficiencies in the range 65.12 ± 1.05% to 69.85 ± 3.2% with desired mean particle size distribution of 101.1 ± 5.9 and 120.2 ± 2.8 nm and zeta potentials of -43.7 ± 4.7 and -62.9 ± 3.5 mV. All the optimized formulations followed Higuchi-matrix release kinetics and when plotted in accordance with the Korsemeyer-Peppas method, the n-value 0.5 < n < 1.0 suggests an anomalous (non-Fickian) transport. Likewise, the PEGylated
liposomes showed greater
tumor growth inhibition on BT-549 and MCF-7 cell lines from in vitro cytotoxicity studies (p < 0.05). Pharmacokinetic study of conventional and PEGylated
liposomes in Wistar rats demonstrated a 3.33- and 20.28-fold increase in AUC(0-∞) values when compared to pure
drug (p < 0.001). Among the formulations, PEGylated
liposomes showed encouraging results by way of their long circulation and sustained delivery properties for effective treatment of
breast cancer.