Nebulized biopharmaceutical inhalation preparations

In recent years, great progress has been made in the research and development of mRNA vaccines or biopharmaceuticals in the field of COVID-19 prevention and treatment. In the field of treatment of respiratory diseases, it has also become a research and development hotspot with its advantages of short development cycle, good effect and safety. . In inhaled preparations, some properties of nucleic acids will affect the effect of aerosolization and thus the effect of treatment.

Naked nucleic acids are electronegative, prone to degradation, and have low cell uptake and transfection efficiency. Therefore, they need to be equipped with appropriate nucleic acid delivery carriers, especially carriers that can protect aerosol delivery and not be destroyed during the aerosol formation process. Can protect drugs from rapid degradation and promote cellular uptake.

A certain shear force will be generated during the atomization process. Choosing a suitable delivery carrier to wrap the nucleic acid can reduce the damage caused by the shear force, maintain good atomization stability, and maintain the particle size and encapsulation rate before and after atomization. Not subject to change. In addition, the shear force generated by the mesh atomizer during the atomization process is lower, and the process of generating aerosol is gentler, which can further reduce this damage.

There is a mucus-ciliary defense mechanism in the airways that can exclude and eliminate foreign bodies. For the human body, these delivered aerosols are foreign bodies. Immune clearance mediated by alveolar macrophage phagocytosis is another major physiological barrier faced by inhaled nucleic acid nanomedicines. After nanoparticles are deposited in the respiratory tract, they first come into contact with the pulmonary surfactant layer. Alveolar macrophages then internalize the foreign particles and digest them in lysozyme-filled vesicles, transporting them to the mucociliary or lymphatic system for clearance. Therefore, in order to prevent the drug particles from being removed before they reach the target area, these two barriers need to be overcome, and the role of the delivery carrier is particularly critical. Currently, inhaled nucleic acid delivery carriers include viral vectors, lipid nanoparticles (LNP), lipid-polymer hybrid nanoparticles (LPN), nanostructured lipid carriers (NLC), cationic polymers, and exosome nanocapsules vesicles, and protein carriers, etc.

Suitable nebulizer delivery device

The particle size of the aerosol is also critical. The aerodynamic particle size of the aerosol formed by atomized nucleic acid nanomedicine must be in the range of 1-5 μm, so that it can settle in the lungs through the branch-like structure of the bronchus. This requires very high performance of the atomizer. If the performance parameters of the atomizer are not ideal, the carrier will be damaged and the nucleic acid will be exposed and destroyed. Generally speaking, the larger the particle size, the less damage to the drug encapsulation efficiency, but at the same time, the effective lung sedimentation may be less. Therefore, a suitable atomization delivery device is very important. Traditional ultrasonic nebulizers and jet nebulizers are no longer so suitable. Even for a mesh atomizer, this requires higher requirements for the machine, which is definitely not something that can be achieved by just any atomizer on the market. This requires the joint efforts of atomizer R&D companies and drug R&D companies.