Nanotechnology-driven therapeutic strategies for lambert–eaton myasthenic syndrome: Emerging drug delivery and immunomodulatory approaches

Lambert–Eaton myasthenic syndrome (LEMS) is a rare autoimmune neuromuscular disorder characterized by impaired acetylcholine release due to autoantibody-mediated targeting of presynaptic P/Q-type voltage-gated calcium channels. Although symptomatic therapies such as amifampridine and immunomodulatory agents provide clinical benefit, their efficacy is limited by short half-life, fluctuating plasma concentrations, systemic toxicity, and dose-dependent adverse effects, including seizures. These limitations highlight the need for advanced drug delivery systems. Recent advances in nanotechnology offer promising strategies to enhance therapeutic precision, bioavailability, and safety in LEMS management. Nanoparticle-based platforms including polymeric nanoparticles and lipid-based nanocarriers enable controlled drug release and improved pharmacokinetic stability, which may help maintain sustained plasma concentrations and thereby enhance drug availability at the neuromuscular junction. In addition, nanocarriers may facilitate improved transport across physiological barriers such as the Blood Nerve Barrier, potentially increasing drug accumulation at presynaptic terminals. Intranasal nanoformulations are explored as a non-invasive systemic delivery strategy, leveraging the highly vascularized nasal mucosa to enhance drug absorption and bypass hepatic first-pass metabolism, thereby improving systemic exposure rather than enabling direct central nervous system targeting. Furthermore, nano-enabled immunomodulation may allow selective suppression of pathogenic autoantibodies while minimizing systemic immunosuppression. This review provides a comprehensive overview of LEMS pathophysiology and current therapies, with a focused discussion on nanotechnology-driven approaches that may overcome existing pharmacological limitations. Future perspectives in targeted delivery, nano-immunotherapy, and biomarker-guided treatment strategies are also highlighted.