The Evaluation of Drug Delivery Nanocarrier Development and Pharmacological Briefing for Metabolic-Associated Fatty Liver Disease (MAFLD): An Update

Abstract

Current research indicates that the next silent epidemic will be linked to chronic liver diseases, specifically non-alcoholic fatty liver disease (NAFLD), which was renamed as metabolic-associated fatty liver disease (MAFLD) in 2020. Globally, MAFLD mortality is on the rise. The etiology of MAFLD is multifactorial and still incompletely understood, but includes the accumulation of intrahepatic lipids, alterations in energy metabolism, insulin resistance, and inflammatory processes. The available MAFLD treatment, therefore, relies on improving the patient’s lifestyle and multidisciplinary pharmacotherapeutic options, whereas the option of surgery is useless without managing the comorbidities of the MAFLD. Nanotechnology is an emerging approach addressing MAFLD, where nanoformulations are suggested to improve the safety and physicochemical properties of conventional drugs/herbal medicines, physical, chemical, and physiological stability, and liver-targeting properties. A wide variety of liver nanosystems were constructed and delivered to the liver, only those that addressed the MAFLD were discussed in this review in terms of the nanocarrier classes, particle size, shape, zeta potential and offered dissolution rate(s), the suitable preparation method(s), excipients (with synergistic effects), and the suitable drug/compound for loading. The advantages and challenges of each nanocarrier and the focus on potential promising perspectives in the production of MAFLD nanomedicine were also highlighted.

Renaming NAFLD to MAFLD: Advantages and Potential Changes in Diagnosis, Pathophysiology, Treatment, and Management

“…MAFLD and T2DM share common pathophysiological features such as IR 1 . Pioglitazone and metformin are effective insulin sensitizers used in T2DM 1,52 .…”

“…There are concerns about the long-term safety of pioglitazone in higher doses 53 . A meta-analysis reported that the use of metformin was critical in improving liver functions and body composition of non-diabetic patients with MAFLD 1 …”

“…Statins are among the most widely prescribed lipid-lowering drugs and are commonly used to manage dyslipidemia 1,56 . In various animal studies, statins were found to mitigate metabolic-associated steatohepatitis-related hepatic lipotoxicity, inflammatory responses, oxidative stress, and fibrosis through multiple pathways 57 .…”

“…A population-based study has also confirmed that a significant proportion of subjects with suspected MAFLD and/or fibrosis have an indication for lipid-lowering therapy due to increased cardiovascular risks and might benefit from statin therapy 58 . Statins have potential antioxidant properties and favorable effects on adiponectin levels, and can reduce the risk of cardiovascular morbidity and mortality in metabolic-associated steatohepatitis and dyslipidemia patients 1,53,59 . Unfortunately, no specific pharmacological treatment has been approved for MAFLD, and current trials for MAFLD or metabolic-associated steatohepatitis drugs are focusing on metabolic pathways to improve dyslipidemia or IR 60 …”

Drug-induced Fatty Liver Disease: Pathogenesis and Treatment

“…11,15 MAFLD is diagnosed in patients when they have the hepatic manifestation of metabolic syndrome, which is diagnosed when three or more of the following conditions are found: high glucose, hypertension, obesity, high triglyceride, and low high-density lipoprotein-cholesterol. 16 There are a growing number of clinical reports proposing that certain drugs can be more hepatotoxic in overweight patients with MAFLD, in contrast with lean patients. 17 DILI in MAFLD appears in two particular clinical situations.…”