Studies on Preparation and Evaluation of Soluble 1:1 Stoichiometric Curcumin Complex for Colorectal Cancer Treatment

This study investigates the complex of curcumin (CMN), which has enhanced solubility and hence, higher cytotoxicity compared to free CMN. Insilco molecular modelling and phase solubility (PS) studies were performed with the drug and carriers for interaction. The complex was characterized by in vitro drug release, FT-IR, PXRD, TGA, DSC, SEM, DLS, and functionalized dyeing test. The result showed that the CMN-PEG6000 complex produced significant properties of solubility (≈ 190 folds) and dissolution (80.68 % at 30 min), with stability constants equivalent to 309 and 377 M-1 at 25 and 37 °C, respectively. It exhibited AL type of isotherm indicating 1:1 stoichiometry. The result from the in vitro cytotoxicity showed that 50 % inhibition (IC50) was achieved on the SW480 and Caco-2 cells at an amount of complex that was considerably lesser than free CMN. Apoptosis study showed that the cells underwent cell death mainly by apoptosis with a small number by necrosis. HIGHLIGHTS Enhanced curcumin solubility up to 190 fold higher than pure curcumin was investigated The phase solubility results of curcumin range from 5.7×10-4 M-1 and 7.8×10-4 M-1 at 25 and 37 °C, respectively First time of novel dyeing test was performed with complex of curcumin, signified its solubility This study provides useful approach for obtaining curcumin products with maximum aqueous solubility GRAPHICAL ABSTRACT

Antioxidant support to ameliorate the oxaliplatin-dependent microglial alteration: morphological and molecular study

Oxaliplatin is a third-generation chemotherapy drug mainly used for colorectal cancer treatment. However, it is also known to trigger neuropathy whose underlying neurobiological mechanisms are still under investigation and currently available treatments show limited efficacy. It is now established that neurons are not the only cell type involved in chronic pain and that glial cells, mainly astrocytes and microglia, are involved in the initiation and maintenance of neuropathy. Among all the pathogenetic factors involved in neuropathic pain, an oxaliplatin-dependent oxidative stress plays a predominant role. In our study, the antioxidant properties of magnesium (Mg), manganese (Mn) and zinc (Zn) salts were evaluated in order to counteract microglial activation induced by oxaliplatin. The antioxidant efficacy of these metals was evaluated by the means of molecular and morphological assays on the BV-2 microglial cell line. Our data clearly show that Mg, Mn and Zn are able to prevent oxaliplatin-dependent microglial alterations by reducing both oxidative and endoplasmic reticulum stress.

Small-molecule inhibitor PD-1/PD-L1 interaction for colorectal cancer treatment

Inhibition of the PD-1/PD-L1 pathway is a target for the development of new therapies. US10710986 patent describes a small molecule that targets PDL-1/PD-1 interactions and triggers antitumor activity against colorectal cancer. However, it does not describe biological assays that allow us to suppose that this small molecule may be active in other types of cancer. So far, there are no reports of clinical trials to evaluate the safety, toxicity and efficacy, but it will be of great interest to analyze in the future if this compound surpasses the action of therapy in cancer.