Nonalcoholic fatty liver disease: Current therapies and future perspectives in drug delivery

Nonalcoholic fatty liver disease (NAFLD) affects approximately 25% of the adult population worldwide. This pathology can progress into end-stage liver disease with life-threatening complications, and yet no pharmacologic therapy has been approved. NAFLD is commonly characterized by excessive fat accumulation in the liver and is in closely associated with insulin resistance and metabolic disorders, which suggests that NAFLD is the hepatic manifestation of metabolic syndrome. Regarding treatment options, the current validated strategy relies on lifestyle modifications (exercise and diet restrictions). Although there are no approved drug-based treatments, several clinical trials are ongoing. Novel targets are being discovered, and the repurposing of drugs that show promising effects in NAFLD is starting to gain more interest. The field of nanotechnology has been growing at an increasing rate, with new and more efficient drug delivery strategies being developed for NAFLD treatment. Nanocarriers can easily encapsulate drugs that need to be better protected from the organism to exert their effect or that need help at reaching their target, thereby helping achieve a better bioavailability. Drug delivery systems can also be designed to target the site of the disease, in this case, the liver. In this review, we focus on the current knowledge of NAFLD pathology, the targets being considered for clinical trials, and the current guidelines and ongoing clinical trials, with a specific focus on potential oral treatments for NAFLD using promising drug delivery strategies.