RESUMEN
Letrozole (LTZ) is used as first-line treatment for hormone-positive breast cancer (BC) in postmenopausal women. However, its poor aqueous solubility and permeability have reduced its clinical efficacy. Herein, we developed LTZ-nanotransferosomes (LTZ-NT) to address above mentioned issues. The LTZ-NT were optimized statistically using Design Expert® followed by their characterization via dynamic light scattering (DLS), Transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and Differential scanning calorimetry (DSC). The optimized LTZ-NT was incorporated into 1% chitosan-gel to develop LTZ-NTG. Moreover, in vitro drug release and ex vivo permeation of LTZ-NTG were performed and compared with LTZ-dispersion and LTZ-NT. Additionally, skin irritability and histopathology of LTZ-NTG were investigated. Furthermore, in vitro antitumor study of LTZ-NTG was investigated in BC cell lines. The optimized LTZ-NT showed suitable zeta potential (30.4 mV), spherical size (162.5 nm), and excellent entrapment efficiency (88.04%). Moreover, LTZ-NT exhibited suitable thermal behavior and no interactions among its excipients. In addition, LTZ-NTG had an optimal pH (5.6) and a suitable viscosity. A meaningfully sustained release and improved permeation of LTZ was observed from LTZ-NTG. Additionally, LTZ-NTG showed significantly enhanced cell death of MCF-7 and MCC-7 cells. It can be concluded that LTZ-NTG has the potential to deliver chemotherapeutic agents for possible treatment of BC.
RESUMEN
This study explored to what extent does reverse culture shock predict the level of anxiety, depression, and psychological well-being among fresh foreign degree holders in Pakistan, in addition to finding out the relationship between the study variables. Participants consisted of 124 fresh foreign degree holders (109 men and 15 women) who were recruited through purposive and snowball sampling techniques. Reverse Culture Shock Scale, Major Depression Inventory, Beck Anxiety Inventory, and WHO-5 Well-being Index were used to measure study variables. Results show that reverse culture shock is a strong predictor of psychological well-being explaining 23% variance in well-being scores of fresh foreign degree holders. As hypothesized, it has positive associations with distress symptoms including anxiety and depression, whereas, a negative correlation was found with psychological well-being and the age of fresh foreign degree holders. However, contrary to the hypothesis, reverse culture shock has no association with time passed since arrival back home and duration of stay abroad.