Design of Potential Pharmaceutical-Based Metal Complexes Derived from Cromolyn a Mast Cell Stabilizer

Abstract

A series of pharmaceutical metal complexes (pMCs) were produced and characterized using the mast cell stabilizer, cromolyn, and bioactive metal ions (Zn +2 , Mg +2 , and Ca +2 ). Three novel pMCs, Cromolyn-Zn, Cromolyn-Mg, and Cromolyn-Ca, were formed through reactions under controlled temperature and pH conditions. Additional characterization for these materials was performed employing a number of solid-state characterization techniques, such as thermogravimetric analysis (TGA), powder and single-crystal X-ray diffraction (PXRD and SCXRD), and scanning electron microscopy coupled with energy-dispersive spectroscopy (SEM-EDS). TGA demonstrated that these metal complexes showed an enhanced thermal stability due to the strong coordination with the ligand, cromolyn. PXRD data indicates a high degree of crystallinity as well as a unique packing arrangement for each pMCs. SEM analysis showed materials with welldefined morphologies, while EDS presented elemental evidence for the unique composition of each pMCs. The crystal structure for these materials was elucidated through SCXRD, and a variety of binding modes and packing motifs were found within each respective metal complex. Only two-dimensional (2D) structures were achieved under the conditions studied. These binding modalities might affect the activity and delivery of cromolyn sodium (CS). The stability of the metal complexes was assessed in phosphate-buffered saline (PBS, pH = 7.40) and fasted-state simulated gastric fluids (FaSSGF, pH = 1.60). Dissolution studies show high stability and slow degradation for the metal complexes, while a higher dissolution was observed for the drug compound in PBS. Neither CS nor the pMCs dissolved significantly in FaSSGF at 37 °C.

Sodium Cromolyn Modulates Carrageenan-Induced Acute Inflammation Through the Interleukin-6 Levels

“…cultured mast cells. Despite this, earlier research on the pharmacological actions of CS demonstrated its ability to inhibit mediator release through mast cells (5). This agent was found to enhance healing and reduce inflammatory responses in the nose, trachea, and lungs by modulating the expression of IL-6, TNF-α, TLR3, and TRIF in a rat model of influenza (30).…”

“…Originally developed for allergic asthma, it has shown potential in managing mastocytosis, allergic skin diseases, and intestinal allergies. Previous research on CS's pharmaceutical effects has shown it suppresses mediators released from mast cells triggered by specific antigens, potentially reducing the activation of other cell types (5)(6)(7). Cromolyn is effective in treating asthma, systemic mastocytosis, aphthous ulcers, and food allergies (8).…”

Cytokine Storm Syndrome in SARS-CoV-2 Infections: A Functional Role of Mast Cells

“…Interestingly, GPR35 mRNA is upregulated upon challenge with IgE antibodies [ 96 ], suggesting that GPR35 may be a potential target for using cromolyn sodium in the treatment of asthma. Previous studies on the pharmacological actions of cromolyn sodium indicate that it prevents the release of mediators from mast cells [ 126 ], although recent studies employing mouse [ 127 ] and human [ 128 ] cultured MCs questioned cromolyn sodium function as a MC stabilizer agent. Regardless, the mechanism of action for this agent has been noted as inhibiting the activity of protein kinase C and transport of chloride into MCs [ 97 ].…”

Statistical Optimization and Evaluation of in Situ Gel for the Ocular Delivery of Cromolyn Sodium

“…Cromolyn sodium works by inhibiting the histamine release from conjunctival mast cells and degranulating sensitized mast cells [5,6]. The biopharmaceutical classification system classifies Cromolyn sodium as a class III compound.…”