###Pulmonary delivery platform for RNA therapeutics – using microfluidic and particle engineering techniques to produce dry powder aerosol for inhalation
Project ID: 2228bd1050 (You will need this ID for your application)
Research Theme: Healthcare Technologies
UCL Lead department: School of Pharmacy
Lead Supervisor: Jenny Lam
Project Summary:
RNA-based medicine has attracted tremendous attention for its diverse therapeutic potential. The major barrier to the translation of RNA therapy from bench to bedside is delivery - to bring the therapeutic RNA to the site of actions in a safe, effective and reproducible manner. RNA is notoriously unstable and cannot permeate through cell membrane. A delivery system is needed to protect RNAs from premature degradation and to promote uptake of RNA to the target cells.
Lung diseases such as respiratory infection, asthma and lung cancer are enormous global health burden. While RNAs are powerful molecules with huge potential for the treatment of these diseases, their administration is limited to parenteral injection, which is invasive and has a poor distribution to the lung. In contrast, pulmonary delivery can increase RNA concentration in the lung to enhance efficacy in a non-invasive manner while minimising systemic exposure and side-effects.
Our group has recently overcome the pulmonary RNA delivery challenges by developing synthetic peptide-based systems which can deliver RNAs to the airways efficiently with no signs of toxicity. We have also demonstrated that spray-drying is a feasible particle engineering technique to produce inhalable RNA powder with good aerosolisation properties. To take this technology further, we need to optimise the preparation method that is suitable for large scale production and to enhance the stability of the formulation to avoid cold-chain storage and provide a good shelf-life. Once established, the formulations will be ready for testing on relevant animal models. The aims of this project include: (i) establishment of an effective method to control the self-assembly of peptide/ RNA complexes using microfluidic technology; (ii) design and optimisation of spray-dried RNA powder formulations with good stability and aerosolisation properties; (iii) evaluation of the optimised RNA powder formulation in animal models for transfection efficiency, safety and pharmacokinetic profile.