A research team from Ludwig-Maximilians-Universität München (LMU) has developed a novel delivery system for inhalable mRNA vaccines. The innovation combines poly(lactic-co-glycolic acid) (PLGA) and poly(β-amino esters) (PBAEs) and is designed to overcome key biological barriers in the lungs.
Details of the study, “A Hybrid Polymer System for Pulmonary mRNA Delivery: Advancing Mucosal Vaccine Development,” were published in Cell Biomaterials.
“Effective mucosal vaccination via inhalation requires carrier systems that can penetrate airway mucus while protecting the fragile RNA molecules they carry,” said research team lead Olivia M. Merkel, PhD, in a university news release.
According to Dr. Merkel, who is chair of drug delivery at LMU, her team engineered the system using a spatiotemporally coordinated mechanism. The hybrid polymer nanocarriers are transported within endosomes (tiny vesicles). Once they’ve advanced through the lung barrier, the nanoparticles are released and deliver the mRNA to the targeted immune cells.
The researchers tested the approach in ex vivo human precision-cut lung slices. The results demonstrated robust immune activation and supported both antigen presentation and immune cell maturation through mRNA expression.
In comparison to clinically approved lipid nanoparticles, Dr. Merkel said the PLGA/PBAE nanocarriers retained higher transfection efficiency after vibrating-mesh nebulization. This highlights the stability, efficiency and suitability of inhaled vaccine applications.
“A major advantage of the new system is its robustness during aerosolization,” she said. “Our findings show that data-driven polymer design can address multiple delivery barriers simultaneously. This hybrid platform offers a promising alternative to lipid nanoparticles for next-generation pulmonary mRNA vaccines.”
