PEGylated liposomes of anastrozole for long-term treatment of breast cancer: in vitro and in vivo evaluation

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?in vitro cytotoxicity studies (p?(0–∞) values when compared to pure drug (p?相似文献   

Sediment-associated contaminants and liver diseases in bottom-dwelling fish

High concentrations of chemicals have been found in sediments from urban areas of Puget Sound. Hundreds, of organic chemicals (including certain aromatic hydrocarbons [AHs] and various chlorinated compounds) were identified. Statistical methods were used to evaluate possible relationships between the chemistry data and fish diseases. Positive correlations were found between the frequencies of liver neoplasms (e.g., hepatocellular carcinoma) and other liver lesions in English sole (Parophrys vetulus) and concentrations of AHs in sediment; such correlations were not found with chlorinated hydrocarbons. Strong evidence was also obtained to show that many organic chemicals in sediment are bioavailable to bottom-dwelling fish. Stomach contents (consisting mainly of benthic invertebrates) from English sole had concentrations of a number of AHs similar to those in the sediment from which the fish were taken. In these same fish, metabolites of many aromatic compounds were found in bile using a procedure combining HPLC with fluorescence detection. Further, the concentrations of certain xenobiotic metabolites in bile were correlated positively with the occurrence of liver neoplasms in English sole.