Utilizing Sphingomyelinase Sensitizing Liposomes in Imaging Intestinal Inflammation in Dextran Sulfate Sodium-Induced Murine Colitis

Abstract

Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the gastrointestinal tract, resulting in severe symptoms. At the moment, the goal of medical treatments is to reduce inflammation. IBD is treated with systemic anti-inflammatory compounds, but they have serious side effects. The treatment that is most efficient and causes the fewest side effects would be the delivery of the drugs on the disease site. This study aimed to investigate the suitability of sphingomyelin (SM) containing liposomes to specifically target areas of inflammation in dextran sulfate sodium-induced murine colitis. Sphingomyelin is a substrate to the sphingomyelinase enzyme, which is only present outside cells in cell stress, like inflammation. When sphingomyelin consisting of liposomes is predisposed to the enzyme, it causes the weakening of the membrane structure. We demonstrated that SM-liposomes are efficiently taken up in intestinal macrophages, indicating their delivery potential. Furthermore, our studies showed that sphingomyelinase activity and release are increased in a dextran sulfate sodium-induced IBD mouse model. The enzyme appearance in IBD disease was also traced in intestine samples of the dextran sulfate sodium-treated mice and human tissue samples. The results from the IBD diseased animals, treated with fluorescently labeled SM-liposomes, demonstrated that the liposomes were taken up preferentially in the inflamed colon. This uptake efficiency correlated with sphingomyelinase activity.

Exploring the Usability of α-MSH-SM-Liposome as an Imaging Agent to Study Biodegradable Bone Implants In Vivo

“…We wanted to assess the success of targeting the liposomes to the macrophages in the implant site. Earlier, it was shown that monocytes; macrophage subtypes M1, M2; and colon cancer cell line Caco-2 effectively take up SM-liposomes in vitro [ 50 ]. However, in bone fraction studies, we wanted to focus on BMDM cells extracted from bone marrow in the rats’ femurs and inducing these BMDMs to macrophage to check the uptake of liposomes.…”

“…The cell nuclei counterstaining was done with a DAPI solution final concentration of 0.1 µg/mL. The procedure has been previously demonstrated successfully [ 50 ].…”

Construction Strategy of Functionalized Liposomes and Multidimensional Application

“…[136] For example, LEE et al [137] used esterase-unstable ester bonds on lipid fractions to attach radiotracers and validated the tracer potential of enzyme-responsive liposomes in specific tumor environments (Figure 8b). Recently, Medina et al [138] successfully constructed a specific liposome targeting the inflammatory region of dextran sodium sulphate-induced colitis in mice by using sphingomyelinase, which is only present extracellularly during cellular stress such as inflammation.…”

Anti-Inflammatory Effect of Topiramate in a Chronic Model of TNBS-Induced Colitis

“…Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal (GI) tract that comprises two primary forms: Crohn’s disease (CD) and ulcerative colitis (UC) [ 1 , 2 , 3 , 4 ]. CD is manifested by a transmural and discontinuous ulceration of any portion of the GI tract, mainly affecting the terminal ileum and the perianal region [ 2 , 4 ].…”