Bhagwati Sharma

Palbociclib (PCB), categorized as a BCS class II drug, is characterized by low aqueous solubility. The drug's limited aqueous solubility and poor dissolution rate pose significant challenges, potentially affecting its absorption and overall therapeutic efficacy. Co-amorphous (CAM) systems have been extensively investigated as a potential solution to overcome the issue of poor water solubility in numerous active pharmaceutical ingredients. This research study hypothesized that the coamorphization process involving the compounds PCB and naringin (NG) would lead to an increase in the aqueous solubility of PCB. Additionally, it was proposed that this process would also enhance the anticancer impact of PCB since NG is recognized for its pharmacological impact on breast cancer cells. In silico studies, it was revealed that PCB could interact with NG via hydrogen bonding. Furthermore, the prepared CAM (PCB-NG-CAM) system using PCB and NG was characterized by PXRD, DSC, FTIR, Raman spectroscopy, solid-state ¹³C nuclear magnetic resonance, and SEM. PCB-NG-CAM exhibited a significant increase in solubility, dissolution rate, and intestinal permeation compared to crystalline PCB. Furthermore, PCB-NG-CAM exhibited excellent physical stability at 40 °C/75% RH for up to 3 months. In addition, PCB-NG-CAM showed superior in vitro efficacy on MDA-MB-231 triple-negative breast cancer cell lines. PCB-NG-CAM resulted in a 2.24 times higher apoptosis rate and a 1.6 times greater ROS production than free PCB. Additionally, the inhibitory effect on cell migration and alterations in MMP was more pronounced in cells treated with PCB-NG-CAM. Therefore, this study indicated that PCB-NG-CAM has the potential to significantly improve the oral administration, solubility, and therapeutic efficacy of PCB.

Utilization of naturally available biomolecules such as nucleosides with several coordination sites as organic counterparts for the synthesis of multifunctional self-assembled metal–organic gels is important, considering the time and efforts required for the design of organic ligands that can coordinate to metal ions, forming a gel. In the present work, inosine, a simple nucleoside has been utilized as a ligand for the generation of a supramolecular metallo-hydrogel through coordination with Zn²⁺ ions in the presence of NaOH. Several spectroscopic, microscopic and rheological investigations have been performed to characterize the formed gel. The obtained metallo-hydrogel is transparent, and the transparency can be tuned depending on the amount of NaOH used. The Zn–inosine metal–organic gel exhibits several functional properties such as self-healing, stimuli responsiveness, thixotropy, and injectability. Furthermore, the freeze-dried Zn–inosine xerogel exhibited selective gelation of water, which has been utilized to separate water from mixtures that include organic solvents (or oils) and water. The semiconducting characteristics of the Zn–inosine metallogel have been used for device fabrication based on the Schottky diode interface between a semiconductor and metal. The fabricated device was found to be photo-responsive in nature and exhibited better device parameters when illuminated with light. The present results are anticipated to lead to the development of newer soft materials constructed using simple biomolecules for environmental and electronic applications.

The interaction of Zn²⁺ ions with pristine guanosine under alkaline conditions results in the formation of stimuli-responsive and self-healing supramolecular hydrogel that can be used for fabricating a thin film device based on a Schottky diode interface between a metal and a semiconductor.

Self-assembled metal-ion cross-linked multifunctional hydrogels are gaining a lot of attention in the fields of biomedical and biocatalysis. Herein, we report a heat-triggered metallogel that was spontaneously formed by the self-assembly of adenosine 5'-monophosphate (AMP) and cobalt chloride, accompanied by a color transition depicting an octahedral to tetrahedral transition at high temperature. The hydrogel shows excellent stability in a wide pH window from 1 to 12. The metallogel is being exploited as a multienzyme mimic, exhibiting pH-responsive catalase and peroxidase activity. Whereas catalase mimicking activity was demonstrated by the hydrogel under neutral and basic conditions, it shows peroxidase mimicking activity in an acidic medium. The multifunctionality of the synthesized metallogel was further demonstrated by phenoxazinone synthase-like activities. Owing to its catalase-mimicking activity, the metallogel could effectively reduce the oxidative stress produced in cells due to excess hydrogen peroxide by degrading H₂O₂ to O₂ and H₂O under physiological conditions. The biocompatible metallogel could prevent cell apoptosis by scavenging reactive oxygen species. A green and simple synthetic strategy utilizing commonly available biomolecules makes this metallogel highly attractive for catalytic and biomedical applications.