Exploiting novel materials to overcome physiological barriers for oral inhalation of biologics

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Biological drugs such as peptides, proteins and antibodies are powerful macromolecules that have been established as important classes of therapeutics for the treatment of various diseases. With their high specificity and potency, it is anticipated that biologics will dominate most pipelines. Due to their high susceptibility to degradation and large molecular size that limits transport across the epithelium, administration of biologics is largely limited to parenteral routes which are invasive and require proper training. Non-invasive approach of delivering biologics is highly sought-after. Oral inhalation holds great promise for delivering biologics because of the large surface area and highly vascularisation of the lungs that enable rapid systemic absorption. This route can also increase drug concentration in the airways, making it suitable for the treatment of lung diseases for local action such as severe asthma, respiratory infections, and lung cancers, which are enormous global health burden. Inhalation is non-invasive with the possibility of self-administration. By formulating biologics in dry powder form the stability of biological formulation is also enhanced. This prolongs product shelf-life, avoids cold-chain, reduces drug wastage and environmental impact. The major challenges of pulmonary delivery of biologics are producing aerosols with excellent aerodynamic properties that allow effective deposition of particles in the airways, overcoming the mucus, surfactant, and immunological barriers along the respiratory tract, while protecting the fragile biomolecules from various kinds of stress and degradation during production and delivery. For delivery into the bloodstream, absorption enhancers are also required to increase the permeability of the epithelial barrier controllably and reversibly. The goal of this project is to develop strategies to overcome these physiological barriers, by utilising novel materials developed by Croda (synthetic/naturally derived lipids, polymers, surfactants, and their combinations) that can stabilise biologics from degradation, promote drug absorption and enhance aerosol performance. Machine learning (ML) and pharmacokinetic (PK) models will be applied to assist formulation development. The objectives of the project are: (1) establish models of mucosal barrier that simulate the human airway permeability profile; (2) investigate the absorption enhancing and protein stabilising effects of a series of novel materials; (3) utilise generative ML models to identify novel materials to improve permeability and stability of biologics; (4) engineering of inhaled biologics formulations using appropriate combination of excipients and particle engineering techniques with scalability; (5) predict the PK profile of the formulations using physiologically based pharmacokinetic (PBPK) model.This project aligns with EPSRC remits to accelerate translation to healthcare applications through predictive pharmaceutical sciences and pharmaceutical process engineering. It employs particle engineering techniques with scalability such as spray drying to prepare powder aerosol of biologics for inhalation; utilises novel material combinations to enhance stability and delivery efficiency of biologics; applies computational tools and modelling to assist formulation development. The ultimate goal is to establish inhaled delivery platform of biologics to produce safe and targeted treatments of diseases with unmet medical needs.