Fluorescent PLGA-CY5 from PolySciTech used in development of nanoparticle therapy for obesity treatment by controlling ‘the munchies’

 

Accumulation of fat in the liver can lead to significant morbidity including cirrhosis, fibrosis, as well as promotion of type 2 diabetes. Cannabinoid receptors in the liver recognize THC and related compounds which increases appetite (i.e. the so-called ‘munchies’ after smoking marijuana). However, these receptors also pick up endocannabinoids, which are similar chemical compounds naturally occurring in the human body. Blocking these receptors in the liver can reduce appetite and treat obesity, however interfering with these receptors in the brain where they are part of the endocannabinoid system can lead to deleterious side effects. Researchers at Obesity and Metabolism Laboratory, The Hebrew University of Jerusalem, and Hadassah Medical School used PLGA-CY5 (Cat# AV034) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop a nanoparticle system to deliver cannabinoid blocker rimonabant in a targeted manner to the liver. This research holds promise to improve therapeutic options for obesity and related morbidity conditions such as diabetes and heart disease. Read more: Hirsch, S., Hinden, L., Naim, M.B.D., Baraghithy, S., Permyakova, A., Azar, S., Nasser, T., Portnoy, E., Agbaria, M., Nemirovski, A. and Golomb, G., 2023. Hepatic targeting of the centrally active cannabinoid 1 receptor (CB1R) blocker rimonabant via PLGA nanoparticles for treating fatty liver disease and diabetes. Journal of Controlled Release, 353, pp.254-269. https://www.sciencedirect.com/science/article/pii/S0168365922007866

“Highlights: Successful hepatic CB1 targeting with rimonabant was achieved using nanotechnology. Rimonabant-encapsulated in nanoparticles does not induce CNS-mediated side effects. Liver-targeted of rimonabant ameliorated hepatic steatosis and insulin resistance. Abstract: Over-activation of the endocannabinoid/CB1R system is a hallmark feature of obesity and its related comorbidities, most notably type 2 diabetes (T2D), and non-alcoholic fatty liver disease (NAFLD). Although the use of drugs that widely block the CB1R was found to be highly effective in treating all metabolic abnormalities associated with obesity, they are no longer considered a valid therapeutic option due to their adverse neuropsychiatric side effects. Here, we describe a novel nanotechnology-based drug delivery system for repurposing the abandoned first-in-class global CB1R antagonist, rimonabant, by encapsulating it in polymeric nanoparticles (NPs) for effective hepatic targeting of CB1Rs, enabling effective treatment of NAFLD and T2D. Rimonabant-encapsulated NPs (Rimo-NPs) were mainly distributed in the liver, spleen, and kidney, and only negligible marginal levels of rimonabant were found in the brain of mice treated by iv/ip administration. In contrast to freely administered rimonabant treatment, no CNS-mediated behavioral activities were detected in animals treated with Rimo-NPs. Chronic treatment of diet-induced obese mice with Rimo-NPs resulted in reduced hepatic steatosis and liver injury as well as enhanced insulin sensitivity, which were associated with enhanced cellular uptake of the formulation into hepatocytes. Collectively, we successfully developed a method of encapsulating the centrally acting CB1R blocker in NPs with desired physicochemical properties. This novel drug delivery system allows hepatic targeting of rimonabant to restore the metabolic advantages of blocking CB1R in peripheral tissues, especially in the liver, without the negative CB1R-mediated neuropsychiatric side effects.”