RESUMEN
Background: The use of tyrosine kinase inhibitors (TKIs) as a treatment for chronic myeloid leukemia (CML) has improved the natural history of the disease and increased the duration of survival. Tyrosine kinase inhibitors represent the success of target therapies that work on molecular targets, although some patients still have therapy failure. Vitamin D has antiproliferative, pro-apoptotic, and anti-angiogenic effects on cells, therefore it can be considered as a potential cancer preventative and treatment agent. Inecalcitol (TX-522) is the 14-epi-analogue of Calcitriol (1,25(OH)2-vitamin D3), and inhibits cancer cell proliferation more effectively than Calcitriol. This study was conducted to evaluate the antiproliferative and synergistic effects of the anticancer drugs Imatinib and Dasatinib in combinations with Inecalcitol on human chronic myeloid leukemia K-562 cells. Method: The growth inhibitory activities of Inecalcitol, Imatinib, Dasatinib, and different combinations of one of the two drugs (Imatinib and Dasatinib) with Inecalcitol, were determined in vitro using MTT assay against K-562 cell line. Results: Inecalcitol, Imatinib, and Dasatinib showed potent antiproliferative activities against K-562 cells with GI50 values of 5.6 µM, 0.327 µM, and 0.446 nM, respectively. Combinations of Imatinib or Dasatinib with different concentrations of Inecalcitol increased significantly the antiproliferative activities and potencies of both drugs (****p < 0.0001), with optimal GI50 values of 580 pM (Imatinib) and 0.51 pM (Dasatinib). Furthermore, the combination treatments showed synergistic interaction between the antileukemic drugs and Inecalcitol, with combination indices (CI) < 1. Conclusion: The study demonstrated that the human chronic myeloid leukemia K-562 cells were subjected to a synergistic growth inhibitory impact when antileukemic drugs (Imatinib or Dasatinib) were combined with Inecalcitol, therefore, it is recommended that these combinations be viewed as promising novel antileukemic medications and used in place of individual medications with lower dosages and negligible side effects in the treatment of CML.
RESUMEN
The respiratory system has generated significant interest as an alternative drug delivery route. However, because of the limitations encountered with the present inhalation devices, alternative options could present an ideal opportunity to enhance therapeutic effectiveness and patient compliance. Vaping devices have been extensively used to deliver nicotine. This manuscript aimed to conduct an in vitro evaluation of the performance of commonly used vaping devices to assess their effectiveness in delivering fluticasone propionate (FP) to the lungs. Vaping devices were assessed for aerodynamic performance using the NGI. The e-liquid containing FP was made using glycerin and propylene glycol. The results showed the superiority of the vape-tank and vape-coil over the vape-pod. The vape-tank delivered the highest amount of nicotine. The e-liquid containing the FP was assessed and the results were compared with a marketed FP pressurized metered-dose inhaler (pMDI). The results of the respirable dose (RD) ranged from 22.10 µg for the vape pod, to 50.38 µg for the vape-tank; whereas the marketed pMDI value was 44.54 µg despite the lower content of FP per actuation in the vaping devices (100 µg versus 125 µg). Interestingly, the vaping devices showed a significantly lower level of oropharyngeal deposition than the pMDI (10% versus 50%), and hence, the potential for fewer side effects than those encountered with the chronic use of inhalers. Despite the effectiveness of the vape tank and coil in delivering a high percentage of FP, which makes them a promising alternative for delivering an effective yet user-friendly dosage of respiratory drugs, their safety and toxicity need to be established.
