Amani E. Alharbi

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.

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.