Harnessing therapeutic potential of bromelain and its nanoformulations: sojourn of pineapple from food to nanomedicine

Background: Bromelain is a proteolytic enzyme obtained from pineapple stems, possessing diverse pharmacological properties such as antioxidant, antidiabetic, anticancer, anti-inflammatory, anthelmintic, cardioprotective, nephroprotective, and antiaging effects. However, its therapeutic potential has been limited due to poor bioavailability and low blood–brain barrier (BBB) permeability. Objectives: This review aims to summarize the therapeutic effects of bromelain, highlight its pharmacological importance, and discuss novel drug delivery system (NDDS)-based nanoformulations developed to enhance its bioavailability and clinical applicability. Methods: Relevant literature was reviewed to collect data on bromelain’s pharmacological activities, limitations in clinical use, and recent advancements in nanoformulation-based delivery approaches. Additionally, available clinical trial data involving bromelain were examined. Results: NDDS-based formulations, including solid lipid nanoparticles, gold nanoparticles, silver nanoparticles, nanoemulsions, and nanostructured lipid carriers, have been shown to improve bromelain’s bioavailability and BBB permeability, thereby enhancing its therapeutic efficacy. Several clinical studies further support its pharmacological potential, though broader investigations remain limited. Conclusion: Bromelain exhibits wide-ranging therapeutic benefits, and NDDS-based nanoformulations provide a promising strategy to overcome its pharmacokinetic limitations. Further clinical research is needed to validate its efficacy and establish its role in pharmaceutical and nutraceutical applications. Our evaluation emphasizes that nano-enabled delivery is the most credible route to consistent pharmacokinetics and effect sizes across indications; however, dose-exposure-response data remain sparse and should be prioritized in upcoming trials.