Nanotechnology-Driven Therapeutic Strategies for Lambert–Eaton Myasthenic Syndrome: Emerging Drug Delivery and Immunomodulatory Approaches

ABSTRACT
Lambert–Eaton Myasthenic Syndrome (LEMS) is a rare autoimmune neuromuscular disorder characterized by impaired acetylcholine release due to autoantibodies targeting presynaptic P/Q-type voltage-gated calcium channels. Although symptomatic therapies such as amifampridine and immunomodulatory agents provide clinical benefit, their therapeutic efficacy is limited by short half-life, systemic toxicity, fluctuating plasma levels, and dose-dependent adverse effects including seizures. These limitations highlight the urgent need for advanced drug delivery systems. Recent advancements in nanotechnology offer promising strategies to enhance therapeutic precision, bioavailability, and safety in LEMS management. Nanoparticle-based drug delivery platforms, including polymeric nanoparticles, lipid-based nanocarriers, and intranasal nanoformulations, enable controlled release, targeted delivery to the neuromuscular system, reduced systemic exposure, and improved pharmacokinetic profiles. Furthermore, nano-enabled immunomodulation may allow selective suppression of pathogenic autoantibodies while minimizing generalized immunosuppression. This review provides a comprehensive overview of LEMS pathophysiology and current therapeutic strategies, with a special focus on emerging nanotechnology-based approaches that hold potential to transform disease management. Future directions in nano-immunotherapy, targeted delivery, and biomarker-guided treatment strategies are also discussed.