Intranasal delivery of bryostatin-1 using surface charge-engineered lipid nanoparticles to modulate mucosal defense...

Allergic rhinitis (AR), driven by immune imbalance and excessive IgE production, manifests with symptoms that significantly impair the patient's quality of life. Current therapies mainly provide symptomatic relief without correcting the underlying immune dysregulation. Bryostatin-1 (bryo-1) is a promising candidate for the causal treatment of AR. It potently inhibits IgE-mediated allergic responses while enhancing nasal mucosal defense through the selective induction of IgA antibodies upon intranasal administration. However, the intranasal delivery of bryo-1 faces challenges, including high cost, chemical instability, and limited permeability across the nasal mucosal barrier. In this study, bryo-1 was incorporated with liposomes with varying surface charges. These LNPs exhibited stronger interactions with antigen-presenting cells and enhanced cellular uptake and delivery efficiency of bryo-1 in vitro. Notably, anionic LNPs achieved superior bryo-1 delivery to B cells, selectively promoting IgA class switching while suppressing IgE expression. In an AR mouse model, even the low-dose (0.5 ng) intranasal administration of bryo-1-loaded anionic LNPs elevated antigen-specific IgA levels in salivary secretions. These findings indicate that anionic LNPs enhance delivery efficiency, representing a promising platform for intranasal bryo-1 delivery to modulate mucosal immunity and treat AR.