To investigate the allelic and genotypic frequencies of the two genetic variations, NC_000006.12: g.160275887C > T (rs662301) and NC_000006.12:g.160231826 T > C (rs315978), in the SLC22A2 gene among the Saudi population. The primary goal is to elucidate potential associations with these genetic variations and the response to metformin therapy over 6 months to enhance our knowledge of the genetic basis of Type 2 Diabetes Mellitus (T2DM) and its clinical management in the Saudi population. 76 newly diagnosed T2DM patients, aged 30 to 60, of both sexes and Saudi origin, were treated with metformin monotherapy. Blood samples were collected before and after 6 months of therapy,80 healthy individuals were included as controls. Genomic DNA was extracted. Genotyping of the SLC22A2 genetic variations was performed using TaqMan® SNP Genotyping Assays. Binary logistic regression was utilized to evaluate how certain clinical parameters influence T2DM concerning the presence of SLC22A2 gene variants. Among these patients, 73.3 % were responders, and 26.7 % were non-responders. For these variants, no statistically significant differences in genotype or allele frequencies were observed between responders and non-responders (p = 0.375 and p = 0.384 for rs662301; p = 0.473 and p = 0.481 for rs315978, respectively). For the SLC22A2 variant rs662301, the C/C genotype was significantly associated with increased T2DM risk with age and elevated HbA1c levels. Similarly, rs315978 revealed higher T2DM susceptibility and HbA1c elevation in C/C genotype carriers, specifically with advancing age compared to individuals with C/T and T/T genotypes. The study offers insights into the genetic landscape of T2DM in Saudi Arabia. Despite the absence of significant associations with treatment response, the study suggests potential age-specific associations, this highlights the complexity of the disease. This research underscores the necessity for expanded research, considering diverse populations and genetic factors, to develop personalized treatment approaches. This study serves as a foundation for future investigations into the Saudi population, recognizing the need for a larger sample size.

Herein, we report on the development of a novel submicron-sized formulation that utilizes the somatostatin receptor agonist, octreotide (OCT), for the solubilization and targeted delivery of paclitaxel (PTX) and docetaxel (DTX) to the cancer cells. The formulation was prepared using a fast, single-step, and scalable method and then, it was characterized in terms of physico-chemical properties and pharmacological activities. Formulation analyses by Electrospray Ionization Mass Spectrometry (ESI-MS) and High-Performance Liquid Chromatography (HPLC) confirmed the successful formation of the formulation and the inclusion of all of its components. Meanwhile, the developed formulation showed acceptable physico-chemical properties with no incompatibilities among its components. In addition, the prepared formulation, OCT-PTX-DTX, demonstrated superior anticancer activities against colorectal carcinoma cell lines compared to the free drugs, with minimal effects on the normal cells. Furthermore, a synergistic anticancer activity of PTX and DTX was enabled by the novel formulation, leading to cell cycle arrest at low drug concentrations. Molecular-based mechanistic investigations verified that OCT-PTX-DTX is taken up by colorectal cancer cells via somatostatin receptors 1 and 2 (SSTR1 and SSTR2), followed by the upregulation of the tumor-suppressor p53/p21 cascade, and the induced cell cycle arrest via suppression of the cell cycle drivers CDK2 and Cyclin A. The formulation reported herein is promising for targeted, biotolerable, and clinically translatable anticancer chemotherapy compared to the commercially available taxane formulations based on surfactants or organic solvents.

Background: Herein, we report on the development of a novel submicron-sized formulation that utilizes the somatostatin receptor agonist, octreotide (OCT), for the solubilization and targeted delivery of paclitaxel (PTX) and docetaxel (DTX) to the cancer cells. The formulation was prepared using a fast, single-step, and scalable method, and then, it was characterized in terms of physicochemical properties and pharmacological activities. Methods: Formulation analyses by Electrospray Ionization Mass Spectrometry (ESI-MS) and High-Performance Liquid Chromatography (HPLC) confirmed the successful formation of the formulation and the inclusion of all of its components. Results: Meanwhile, the developed formulation showed acceptable physicochemical properties with no incompatibilities among its components. In addition, the prepared formulation, OCT-PTX-DTX, demonstrated superior anticancer activities against colorectal carcinoma cell lines compared to the free drugs, with minimal effects on the normal cells. Furthermore, a synergistic anticancer activity of PTX and DTX was enabled by the novel formulation, leading to cell cycle arrest at low drug concentrations. Conclusions: Molecular-based mechanistic investigations verified that OCT-PTX-DTX is taken up by colorectal cancer cells via somatostatin receptors 1 and 2 (SSTR1 and SSTR2), followed by the upregulation of the tumor-suppressor p53/p21 cascade, and the induced cell cycle arrest via suppression of the cell cycle drivers CDK2 and Cyclin A. The formulation reported herein is promising for targeted and biotolerable anticancer chemotherapy compared to the commercially available taxane formulations based on surfactants or organic solvents.