A research team from Harbin Institute of Technology, Shenzhen Vocational and Technical College and Shenzhen People's Hospital has developed an alternative nebulizer platform that uses surface acoustic waves (SAW), according to Memes Consulting. They demonstrated that SAW nebulization can generate aerosols of suitable concentration and particle size distribution, which can be effectively inhaled and administered into the lungs, and is a potential nebulizer device for the treatment of asthma. In this study, the researchers proposed a method to achieve drug atomization through microfluidic channels. The method uses photolithography to prepare SU-8 microchannels on the surface of piezoelectric substrates. The closed microfluidic channel was prepared by combining the silica coating process and the PDMS (polydimethylsiloxane) process to provide continuous atomization of the drug to improve the deposition efficiency of the microfluidic drug atomization.

Schematic diagram of fabrication of SAW device based on SU-8 microchannel

There are two main routes for drug delivery to the lungs, one is the local action of the drug on the surface of the lung along the respiratory tract; the other is the drug is transported to the whole body through the blood. Nearly 50 years of documented use of the former shows a significant increase in the use of the former, with the realization that local patient treatment, albeit relatively less efficient, requires significantly lower levels of drug dosage, side effects and toxicity compared to oral or systemic administration. There are relatively few problems.

Currently, inhalation therapy is widely used to treat respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, and pulmonary hypertension. Delivering the drug directly to the lungs by inhalation facilitates locally targeted treatment of disease or specific damaged areas, and the drug is inhaled painlessly, minimizing potential systemic side effects.

Asthma is a chronic inflammatory disease associated with excess lymphocytes and eosinophils in the walls of the airways. This airway inflammation narrows the airways, causing airflow obstruction when the body breathes. For inhalation therapy to be most effective, drug-laden aerosols must be deposited primarily at the site of inflammation in the lungs. Recent studies have shown that hypereosinophils are found throughout the lung area, from the bronchi to the alveoli, in certain types of asthma patients. Therefore, direct deposition of drugs throughout the lower respiratory tract is considered the most effective treatment.

One of the most critical factors affecting pulmonary deposition of particles or aerosols is the aerodynamic properties of the particles, including particle or aerosol size, density, shape, hygroscopicity, etc. Numerous clinical studies have shown that nebulized aerosol size is critical to the efficacy of inhalation therapy. Generally speaking, the larger the aerosol particle size, the easier it is to deposit in the upper respiratory tract and even the extrathoracic area. When exhaling, aerosols with smaller diameters can be quickly exhaled, with particle sizes as small as 0.5 μm. At present, many studies have shown that during normal tidal breathing, the particle size of the aerosol is 1-5 μm, which is the optimal range for pulmonary administration.

Compared to traditional metered dose inhalers (MDIs) and dry powder inhalers (DPIs), the nebulizers run longer and deliver more medication. Also, unlike metered-dose inhalers, this nebulizer does not require patient coordination skills, nor is it required to be actuated by inhalation like dry powder inhalers, which may be helpful for those with chronic obstructive pulmonary disease exacerbations or asthma attacks. It is urgently needed for patients who cannot self-medicate. Similarly, ordinary inhalers are less practical among children and elderly patients, and the dose in this nebulizer can be adjusted according to age and gender.

To address the various technical issues of drug delivery listed above, the researchers developed a SAW nebulization platform based on microfluidic fluid delivery. SAW is an acoustic wave propagating along the surface of a piezoelectric substrate with an amplitude on the nanometer scale. Compared with traditional ultrasonic atomization (frequency less than 1 MHz), SAW atomization has a higher driving frequency (frequency greater than 10 MHz), which can produce a large amount of aerosols with particle sizes in the range of 1–10 μm. SAW is an efficient way to transfer mechanical energy to fluids. Unlike ultrasound, which propagates energy as a whole, SAW transmits energy that is immobilized on the substrate until it comes into contact with the fluid. When a droplet is placed on the path of SAW propagation, the SAW will decay into a leaky surface acoustic wave (LSAW) mode when it reaches the boundary between the substrate and the liquid. As the wave decays, acoustic energy leaks into the droplet at an oblique angle known as the "Rayleigh angle." This process creates acoustic radiation pressure and circulating flow in the droplet, known as surface acoustic wave flow, as shown in the figure below.

The upper figure is a schematic diagram of the SAW interacting with the liquid to generate atomization; the lower figure is the piezoelectric substrate (left) for generating the SAW and the portable battery-powered circuit (right) for generating the SAW.

An ideal nebulizer can efficiently deliver high doses of drugs with precise control of droplet size distribution. Furthermore, SAW nebulization has been shown to have a wide range of applications, such as protein extraction, characterization of paper-based analytical devices for diagnostics, drug delivery, mass spectrometry, spray cooling, and more. Anushi E Rajapaksa et al. reported plasmid DNA droplets produced by a SAW hand-held nebulizer in a size range suitable for delivery to the lower respiratory tract. Layla Alhasan et al. demonstrated that the SAW nebulization platform is a promising and efficient method for the delivery of lung stem cells. Therefore, these studies confirmed that SAW nebulization can deliver drugs with droplets of 1–5 μm in diameter to deep lung regions.

Image captured by a high-speed camera of SAW-wave nebulized salbutamol solution based on SU-8 microfluidic feed (surface acoustic wave frequency 60 MHz, input power 5.26W)

Using a novel microfluidic fluid delivery method, the researchers atomized the salbutamol solution into tiny droplets, forming an almost ideal aerosol plume with no jetting in the process. Nebulizing salbutamol solution using the SAW device based on the SU-8 microfluidic fluid supply resulted in a deposition rate of 75% in the lung area, significantly higher than the 46% typically achieved with medical nebulizers. The difference was statistically significant (P <>

Paper link:

https://www.nature.com/arTIcles/s41598-022-11132-9

Editor: Huang Fei

Leave a Reply

Your email address will not be published.