Benign prostatic hyperplasia is one of the most predominant health disorders in men with increasing incidence by age and usually accompanied with other bothersome symptoms. A new fixed dose combination, containing Silodosin and Solifenacin, has been recently launched for relieving such disorder associated with overactive bladder syndrome. In the current work, three smart, innovative and white spectrophotometric methods have been newly developed and optimized for simultaneous determination of the studied drugs in their binary mixture using water as an eco-friendly solvent. The adopted strategy relied on calculation of one or two factors as numerical constant or spectrum allowing mathematical filtration of desired analyte and full removal of any overlapped components in the mixture. The developed methods are categorized over two spectrophotometric platform windows. Window I deals with absorption spectra in its native forms (zero-order) including a newly developed method termed induced concentration subtraction (ICS) as well as induced dual wavelength (IDW) methods. Whereas window III is concerned with ratio spectra as in induced amplitude modulation (IAM) method. Compared to classical spectrophotometric methods, the proposed ones are superior in overcoming the inherited challenges in zero-order absorption spectrum of Solifenacin, particularly its very low absorptivity and lack of unique absorption maximum. Validity of the methods were thoroughly assured as per ICH guidelines with unified regression over 3.0-50.0 µg/mL in ICS method while IDW and IAM ones possessed linearity ranges of 3.0-50.0 µg/mL of Silodosin and 5.0-60.0 µg/mL of Solifenacin. The work was also extended to verify content uniformity of dosage units in accordance with USP recommendations. Greenness profile of the proposed methods was clearly assessed, in comparison to the reported analysis ones, via state-of-the-art software metrics, namely, green solvent selection tool (GSST), complementary green analytical procedure index (ComplexGAPI) and analytical greenness (AGREE). Finally, the proposed methods were in good adherence to the recently published postulates of white analytical chemistry.

Benign prostatic hyperplasia is one of the most predominant health disorders in men with increasing incidence by age and usually accompanied with other bothersome symptoms. A new fixed dose combination, containing Silodosin and Solifenacin, has been recently launched for relieving such disorder associated with overactive bladder syndrome. In the current work, three smart, innovative and white spectrophotometric methods have been newly developed and optimized for simultaneous determination of the studied drugs in their binary mixture using water as an eco-friendly solvent. The adopted strategy relied on calculation of one or two factors as numerical constant or spectrum allowing mathematical filtration of desired analyte and full removal of any overlapped components in the mixture. The developed methods are categorized over two spectrophotometric platform windows. Window I deals with absorption spectra in its native forms (zero-order) including a newly developed method termed induced concentration subtraction (ICS) as well as induced dual wavelength (IDW) methods. Whereas window III is concerned with ratio spectra as in induced amplitude modulation (IAM) method. Compared to classical spectrophotometric methods, the proposed ones are superior in overcoming the inherited challenges in zero-order absorption spectrum of Solifenacin, particularly its very low absorptivity and lack of unique absorption maximum. Validity of the methods were thoroughly assured as per ICH guidelines with unified regression over 3.0-50.0 µg/mL in ICS method while IDW and IAM ones possessed linearity ranges of 3.0-50.0 µg/mL of Silodosin and 5.0-60.0 µg/mL of Solifenacin. The work was also extended to verify content uniformity of dosage units in accordance with USP recommendations. Greenness profile of the proposed methods was clearly assessed, in comparison to the reported analysis ones, via state-of-the-art software metrics, namely, green solvent selection tool (GSST), complementary green analytical procedure index (ComplexGAPI) and analytical greenness (AGREE). Finally, the proposed methods were in good adherence to the recently published postulates of white analytical chemistry.

BACKGROUND: The tumour microenvironment (TME) of head and neck squamous cell carcinoma (HNSCC) consists of different subtypes of cells that interact with the tumour or with each other. This study investigates the possibility of co-culturing HNSCC cells with different stroma cells in a zebrafish xenograft model, focusing on the effect of stroma cells on HNSCC growth and response to irradiation.

MATERIAL AND METHOD: HNSCC metastatic cell line HSC-3 was used along with five types of stroma cells: normal gingival fibroblasts (NOF), cancer associated fibroblasts (CAF), macrophages, CD4 T cells, and human umbilical vein endothelial cells (HUVEC). The mixture of HSC-3 cells and each-stroma cell type-was injected into 2-day post-fertilization zebrafish embryos, and the effect of stroma cells on tumour growth was tested. The study also aimed to mimic the HNSCC tumour by injecting a mixture of HSC-3 cells, CAFs, macrophages, and HUVECs into zebrafish embryos and testing the effect of these stroma cells on the cancer cells' response to irradiation compared to HSC-3-only tumours.

RESULTS: CAFs had a significant inducement effect on tumour size, while HUVECs showed the opposite effect. The irradiated group of HSC-3-only tumour had a significantly smaller tumor cell area compared to the control, while the group with stroma cells and HSC-3 cells showed cancer cells being resistant to irradiation.

CONCLUSION: This is the first report of co-culturing cancer cells with several types of stroma cells using a zebrafish xenograft model. This study also highlighted the role of stroma cells in turning the cancer cells from radioresponsive to radioresistant.