PEGylated liposomes of anastrozole for long-term treatment of breast cancer:in vitroandin vivoevaluation

Abstract

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.

Nanomedicine of anastrozole for breast cancer: Physicochemical evaluation, in vitro cytotoxicity on BT-549 and MCF-7 cell lines and preclinical study on rat model

“…Similarly, enhanced cytotoxic effects upon treatment with nanoparticles may be due to the enhanced drug uptake into the cancer cells due to enhanced permeability retention (EPR) effect. Interestingly, there is a change in the cytotoxic behavior for different polymeric nanoparticles which depends upon drug release behavior and treatment duration [5,16,41].…”

“…Cytotoxic effect of pure drug (anastrozole) and optimized nanoparticulate formulations (ANP-10, ANL-10, and ANC-10) on human breast cancer cell lines (BT-549 and MCF-7) was determined by MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay [5,18]. Briefly, cells were cultured in Dulbecco's modified essential medium (DMEM) with 10% fetal bovine serum (FBS) containing penicillin (100 units/mL) and streptomycin (100 μg/mL).…”

“…These depot types of formulation are intended to contain multiple doses of the drug and upon parenteral administration, release the drug slowly for a prolonged period of time depending on the biodegradable nature of the polymer used. In our earlier reports, anastrozole microspheres and liposomes were prepared successfully using chitosan and lipids as carrier system [4,5].…”

Anastrozole as aromatase inhibitor – new approaches to breast cancer treatment in postmenopausal women

“…Any information available so far shall cover only in vitro studies involving cancer cell lines. Results of studies involving animals are also available [32].…”

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“…Before the advent of anti-human epidermal growth factor receptor 2 (HER2) therapies, the survival of metastatic HER2positive breast cancer patients was quite poor 13 . The advent of targeted therapies has led to impressive improvements in survival 14 . Tamoxifen has been a standard first-line endocrine therapy for postmenopausal women with hormone-responsive advanced breast cancer, but more than half of patients fail to respond and time to progression is less than 12 months in responders.…”