Acu-Flow is unlocking the delivery of the next generation of inhaled drugs for patients with respiratory disorders. According to the World Health Organisation, respiratory diseases (e.g. asthma/chronic obstructive pulmonary disorders (COPD)) are the leading causes of death and disability in the world. In the UK, the British Lung Foundation estimates 1 in every 5 people will be affected by a lung disorder during their life with annual costs of £9.9bn to the NHS. To combat respiratory disorders in patients with poor lung function and acute disease exacerbation, 200 doses of drugs are nebulised each second, globally. Nebulisation is useful to deliver drugs directly to lungs and maximises drug delivery efficiency, while minimising systemic exposure. Different respiratory disorders require drug deposition at different depths within the pulmonary systems. Current nebulisers can achieve droplet sizes of 5-7µm, which are required for treatments within major bronchi (e.g. treatment of asthma/fungal diseases). However, for other diseases, the droplet size must be reduced (e.g. treatment of COPD requires 3-5µm and pulmonary hypertension/emphysema, <3µm). This IUK project will develop a new device with the ability to tune the droplet size (using software control of electronic functionalities in the transducer) enabling different droplet sizes of the drug formulation to be optimised to maximise treatment efficacy. To achieve this, we will partner with pharmaceutical companies to co-produce drug-device combinations of existing and hard-to-nebulise new drugs (e.g. biologics) to enable more effective drug delivery at the intended site in the lungs. The platform has already demonstrated its capability to nebulise a wide range of therapeutics using different (independent) prototype designs for each target, including existing drugs and emerging "high-value" biologics and nanomedicines. The device tunability now being proposed is a highly sought-after feature, as per our discussions with leading clinicians and key opinion leaders in the pharmaceutical industry. Our current InnovateUK Biomedical Catalyst (ending/Q1-2024) helped develop our initial prototypes and establish working relationships with leading pharmaceutical companies and identified a unique ability to tune droplet sizes. We now propose to create bespoke drug-device combinations by developing this tuning ability to target the correct region of the lungs for our partner pharmaceutical companies and lock their drug into our device. In future these drug-device combinations will be tested in clinical trials and following regulatory approval, will be available for patients for effective treatment of a wide array of respiratory disorders.

Acu-Flow is developing a new nebuliser device to enable inhalation for precise and efficient delivery of medicines to the lungs. According to the World Health Organisation, respiratory diseases (e.g. asthma and chronic obstructive pulmonary disorders) are the leading causes of death and disability in the world. In the UK, the British Lung Foundation estimates that 1 in every 5 people in the UK will be affected by a lung disorder during their life with annual costs of £9.9bn to the NHS. These disorders are usually treated by the inhalation of aerosols, where the effective delivery of medication is crucially dependent upon the droplet size distribution. Large drops are caught in the upper respiratory tract, while smaller ones are exhaled before they can be adsorbed - neither reach the patient. Nebulisers are mainly used by very young and old patients, as well as people with poor lung function or in acute exacerbation. They are also becoming important in enabling new drugs for COVID-19 treatment, reshaping the market. Despite advances in the current state-of-the-art nebuliser technology, there are still two key technical constraints that limit the benefits to patients, namely (i) a limited range of acceptable formulation properties; and (ii) relatively inefficient drug delivery. These limitations result in patients needing specific nebulisers for each drug, with many individuals with chronic diseases requiring at least two devices. This can lead to long delivery times (e.g. people with cystic fibrosis can spend 20min nebulising and 20min cleaning the devices, six times/day), leading to challenges in adherence to treatment. It also restricts the adoption of new drugs and vaccines, which have promising potential in treating difficult diseases. Acu-Flow will work with Glasgow University and NIHR Devices for Dignity centre to develop essential technologies and designs to enhance the user-adherence and provide useful data to healthcare providers, enhancing the clinical outcome. This platform uses a unique method, based on the interactions between acoustics, microstructured arrays and liquids, to control droplet size in the aerosols generated, within the clinically effective ranges, with a proven ability to enable precise delivery. The platform has already demonstrated its capability to nebulise a wide range of therapeutics including existing drugs and emerging "high-value" biologics and nanomedicines, which will be critically important in new treatments. This new technology promises broad societal, economic and health impacts for patients, carers, clinicians and the UK economy.

Acu-Flow will develop a new, unique innovative functionality for its new nebuliser platform to enable inhalation delivery of liquid formulations for the precision delivery of medicines to the lungs. According to the World Health Organisation, respiratory diseases are known as the leading causes of death and disability in the world, with an estimated clinical cost of €400bn/year. In the UK, the British Lung Foundation estimates that 10,000 people are diagnosed with a lung disorder every week with a £9.9bn direct cost for NHS and £1.2bn cost to the wider economy. Generally, patients with such respiratory diseases are treated by the inhalation of aerosols, where the effective delivery of medication is crucially dependent upon the droplet size distribution. Larger drops are caught in the upper respiratory tract, while smaller ones are exhaled before they can be adsorbed - neither reach the patient. Nebulisers are also becoming important in enabling new drugs for COVID-19 treatment, reshaping the market. For example, 29 (of 48) drugs in development for COVID-19 are delivered by inhalation, including the recently successful drug by Synairgen. Despite advances in the current state-of-the-art nebuliser technology (including both jet and mesh systems), there are still two key technical constraints that limit the benefits to patients, namely (i) a limited range of acceptable formulation properties; and (ii) relatively inefficient delivery. These limitations result in patients needing specific nebulisers for each drug, with many individuals with chronic diseases requiring different ones. The low efficiency can lead to long delivery times (e.g. people with cystic fibrosis (CF) can spend 20min nebulising and 20min cleaning the devices, six times per day), leading to challenges in adherence to treatment. These limitations also restrict the adoption of new drugs and vaccines, which have promising potential in treating difficult diseases. Working with the University of Glasgow, Acu-Flow will develop essential technologies required to demonstrate its new nebuliser platform. This platform uses a unique method, based on the interactions between acoustics, microstructured arrays and liquids, to control droplet size in the aerosols generated, within the clinically effective range, with a proven ability to enable further precision of delivery. The platform has already demonstrated its capability to nebulise a wide range of therapeutics including existing drugs and emerging "high-value" biologics and nanomedicines, which will be critically important in new treatments e.g. for lung hypertension, CF and tuberculosis, but are not able to reach the market due to the limitations of existing nebulisation platforms. The new system will be a low-cost, portable device with increased efficiency of drug delivery. This new technology promises broad societal, economic and health impacts for patients, clinicians and the UK economy. Although our near-term focus is in drug delivery, we envisage that the technology will provide a generic platform for "smart" droplet generation, with wider potential applications in other important large markets including cosmetics, food formulation and spray-coating.