Effect of Polysaccharide Sulfate-Loaded Poly(lactic-co-glycolic acid) Nanoparticles on Coronary Microvascular Dysfunction of Diabetic Cardiomyopathy.

Abstract

Diabetic cardiomyopathy (DCM) mainly results from development of coronary microcirculatory dysfunction (CMD). Polysaccharide sulfate (PSS), as one heparin drug, has a variety of biological activities. This study examined the efficacy of a new type of PSS-loaded poly lactic-co-glycolic acid (PLGA) nanoparticles (PSS-NPs) on DCM, in finding a theoretical basis for CMD treatment. After establishment of DCM model, the animals were administrated with PSS, PSS-NPs, normal saline or poly(ethylene glycol)1 (PEG1) through intraperitoneal injection. 8 weeks after injection of streptozotocin (STZ), heart function of rats was assessed by echocardiography. The rat tissues were collected and detected by histological analysis. Quantitative reverse transcription PCR (RT-qPCR) and Western blot analyses determined the levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and pro-inflammatory factors. PSS-NPs had a good protective effect on cardiac insufficiency in rats. Administration of PSS-NPs prolonged survival state, and enhanced cardiac function, thereby alleviating the symptoms, and inducing formation of micro vessels. Importantly, it improved the symptoms of DCM patients and their quality of life. Moreover, pro-inflammatory factor levels decreased upon the treatment, accompanied with inactivation of NF-κB signaling pathways, thereby improving DCM. This study demonstrated that the PSS-NPs significantly relieved DCM and restored cardiac function in rats through NF-κB signaling pathways, providing a theoretical basis for development of PSS-NPs, and new treatment ideas for CMD of DCM.