Liposomal glutathione outperforms plain glutathione in uptake, cell regeneration and systemic availability: evidence from cellular and human models

Glutathione is a key intracellular antioxidant involved in redox balance, detoxification and immune support. However, oral glutathione supplementation is limited by poor bioavailability due to gastrointestinal degradation and low membrane permeability. Liposomal formulations offer a promising strategy to enhance delivery and therapeutic efficacy. This study aimed to compare the biological activity and systemic availability of a novel liposomal glutathione formulation (LipoDuo™ Glutathione) with plain glutathione using both <i>in vitro</i> cellular models and <i>in vivo</i> human pharmacokinetic evaluation. Human embryonic kidney 293T cells were treated with LipoDuo™ or plain glutathione to assess intracellular uptake, optimal dosing, cell proliferation and wound healing. In a parallel-arm, open-label human study, twelve healthy subjects (<i>n</i> 6 per group) received a single oral dose of either LipoDuo™ or plain glutathione (1 g), and plasma glutathione levels were monitored over 24 h using LC-MS/MS. Uptake: LipoDuo™ demonstrated ∼1·9-fold higher cellular uptake than plain glutathione, peaking at 6 h (45 % <i>v</i>. 23 %). Proliferation: LipoDuo™ increased cell proliferation by up to 3-fold over control, superior to plain glutathione. Wound healing: LipoDuo™ achieved 100 % closure at 24 h, <i>v</i>. 59·8 % for plain glutathione. Pharmacokinetics: LipoDuo™ achieved a maximum plasma concentration of ∼1800 ng/ml (6× higher than plain), showed a bimodal absorption pattern and maintained plasma levels > 500 ng/ml at 24 h. LipoDuo™ Glutathione significantly improves cellular delivery, biological activity and systemic bioavailability compared with conventional glutathione. Its bimodal distribution and prolonged plasma retention position it as a next-generation antioxidant supplement with clinical potential in oxidative stress management, skin health and metabolic recovery.