The microbiota-gut-brain axis (MGBA) represents a sophisticated communication network between the brain and the gut, involving immunological, endocrinological, and neural mediators. This bidirectional interaction is facilitated through the vagus nerve, sympathetic and parasympathetic fibers, and is regulated by the hypothalamic-pituitary-adrenal (HPA) axis. Evidence shows that alterations in gut microbiota composition, or dysbiosis, significantly impact neurological disorders (NDs) like anxiety, depression, autism, Parkinson's disease (PD), and Alzheimer's disease (AD). Dysbiosis can affect the central nervous system (CNS) via neuroinflammation and microglial activation, highlighting the importance of the microbiota-gut-brain axis (MGBA) in disease pathogenesis. The microbiota influences the immune system by modulating chemokines and cytokines, impacting neuronal health. Synbiotics have shown promise in treating NDs by enhancing cognitive function and reducing inflammation. The gut microbiota's role in producing neurotransmitters and neuroactive compounds, such as short-chain fatty acids (SCFAs), is critical for CNS homeostasis. Therapeutic interventions targeting the MGBA, including dietary modulation and synbiotic supplementation, offer potential benefits for managing neurodegenerative disorders. However, more in-depth clinical studies are necessary to fully understand and harness the therapeutic potential of the MGBA in neurological health and disease.
The objective of the present study was to investigate the potential use of solid lipid nanoparticles (SLNs) as a drug delivery system to enhance the brain-targeting efficiency of rosmarinic acid (RA) following intranasal (i.n.) administration. The RA-loaded SLNs was prepared by the hot homogenization technique, in which glycerol monostearate (GMS) as lipid, tween 80 and soya lecithin were used as surfactant along with hydrogenated soya phosphatidyl choline (HSPC) as a stabilizer, and were characterized for particle size, zeta potential (ZP), in vitro study. Nasal delivery of the developed formulation followed by the study of behavioral (locomotor, narrow beam, body weight) and biochemical parameters (glutathione, lipid peroxidation, catalase and nitrite) in wistar rat was carried out. Optimized RA-loaded SLNs using tween 80 (SLNPRT) have the mean size of (149.2 ± 3.2 nm), ZP (-38.27 mV) entrapment efficiency (61.9 ± 2.2%). 3-NP-treated rat significantly increased behavioral alterations, oxidative damage as compared with the control group. SLNPRT treatment significantly improved behavioral abnormalities and attenuated the oxidative stress in 3NP-treated rats. However, the nasal delivery of SLNPRT produced significant therapeutic action as compared to intravenous application. In the organ distribution study, brain drug concentration was found to be 5.69 µg, in pharmacokinetic study Cmax, tmax, t1/2, AUC values were found to be 0.284 µg/ml, 1.5 h, 3.17 h, and 1.505 µg/ml/h, respectively. The encouraging results confirmed the developed optimized RA-loaded SLNs formulation following the non-invasive nose-to-brain drug delivery that is a promising therapeutic approach for the effective management in Huntington disease.
Ulcerative colitis is the chronic relapsing multifactorial gastrointestinal inflammatory bowel disease, which is characterized by bloody or mucus diarrhea, tenesmus, bowel dystension, anemia. The annual incidence of ulcerative colitis in Asia, North America and Europe was found to be 6.3, 19.2 and 24.3 per 100,000 person-years. The major challenge in the treatment of ulcerative colitis is appropriate local targeting and drug related side-effects. To overcome these challenges, microparticulate systems seem to be a promising approach for controlled and sustained drug release after oral administration. The main goal of this article is to explore the role of microparticles in ulcerative colitis for the appropriate targeting of drugs to colon. There are different approaches which have been studied over the last decade, including prodrugs, polymeric approach, time released system, pH sensitive system, which show the site specific drug delivery to colon. Among these approaches, microparticulate drug delivery system has been gaining an immense importance for local targeting of drug to colon at a controlled and sustained rate. Combined approaches such as pH dependent and time dependent system provide the maximum release of drug into colon via oral route. This article embraces briefly about pathophysiology, challenges and polymeric approaches mainly multiparticulate systems for site specific drug delivery to colon in sustained and controlled manner so that drug related side-effects by reducing dosage frequency can be minimized.
Ulcerative colitis (UC) is presently considered a multifactorial pathology, which may lead to persistent inflammatory action of the gastrointestinal tract (GIT) because of an improperly managed immunological reactivity to the intestinal microbiota found in the GIT. The immune response to common commensal microbes plays an essential role in intestinal inflammation related to UC synbiotics, and it is an important element in the optimal therapy of UC. Therefore, synbiotics, i.e., a mixture of prebiotics and probiotics, may help control the diseased state. Synbiotics alleviate the inflammation of the colon by lowering the reactive oxygen species (ROS) and improving the level of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD). Prebiotic supplementation is not a common practice at the moment, despite numerous research findings proving that the benefits of both probiotics and prebiotics encourage their continued existence and positioning in the GIT, with positive effects on human health by managing the inflammatory response. However, the fact that there have been fewer studies on the treatment of UC with different probiotics coupled with selected prebiotics, i.e., synbiotics, and the outcomes of these studies have been very favorable. This evidence-based study explores the possible role of ROS, SOD, and synbiotics in managing the UC. The proposed review also focuses on the role of alteration of gut microbiota, antioxidant defense in the gastrointestinal tract, and the management of UC. Thus, the current article emphasizes oxidative stress signaling in the GI tract, oxidative stress-based pathomechanisms in UC patients, and UC therapies inhibiting oxidative stress’ effects.
25 May 2022 in Advances in Cancer Biology - Metastasis