Polyphenol-Loaded Liposomal Nanocarriers from Marrubium vulgare: A Promising Nutraceutical Delivery System with Enhanced Bioactivity and Safety

Marrubium vulgare L. aerial parts are a rich source of polyphenols with recognized antioxidant and anti-inflammatory properties; however, their therapeutic potential is limited due to poor stability and bioavailability. To enhance its pharmacological efficacy, a liposomal formulation of M. vulgare polyphenolic extract (MV-Lipos) was developed in this study by employing the thin-film hydration method. Before encapsulating, the free-extract (MV-Ext) was analyzed using LC-MS, and the resultant nanoliposomes were tested for physicochemical qualities, biological activity, and safety. MV-Lipos exhibited particle sizes ranging from 127 to 200 nm, an 84% encapsulation efficiency, and high colloidal stability (zeta potential −29.58 ± 0.40 mV). In vitro evaluations revealed anti-inflammatory and antioxidant activities without cytotoxic effects. In vivo, MV-Lipos significantly improved analgesic and anti-inflammatory responses. Specifically, a dose of 100 mg/kg lowered acetic acid induced writhing by up to 75.9% and carrageenan induced paw edema by 72%, with efficacy comparable to ibuprofen. A 28-day subacute toxicity assessment found no treatment-related adverse effects. Furthermore, molecular docking analyses validated the experimental results by revealing possible interactions with inflammation-related targets. Overall, liposomal encapsulation improved the biological efficacy and safety profile of M. vulgare polyphenols, highlighting their potential as natural agents for the management of pain and inflammatory conditions.