Ahmad is a Pharmacist and a PhD student in the group of Prof. Sally-Ann Cryan at the Royal College of Surgeons in Ireland (RCSI) – School of Pharmacy and biomolecular sciences. In 2019, he received the Strategic Academic Recruitment (StAR) PhD scholarship from the Royal College of Surgeons in Ireland. His PhD work focuses on developing inhalable All Trans Retinoic Acid-loaded nanoparticles as host directed immunotherapy for tuberculosis in collaboration with St. James’ hospital (Trinity College Dublin), Imperial College London and Aerogen Ltd.

He completed his Erasmus Mundus Joint Master’s degree in Nanomedicine for drug delivery (NANOMED EMJMD) jointly from four universities; University of Paris and University of Angers in France, University of Pavia in Italy and University of Patras in Greece, funded by Erasmus+ scholarship. He did his Master’s thesis at Queen’s university Belfast in United Kingdom focusing on engineering targeted nanomedicines for advanced prostate cancer. He obtained his BSc in Pharmacy from the University of Jordan in 2016.

Project summary

Ending Tuberculosis (TB) by 2030 was listed in the UN sustainable development goals as TB kills more people globally than any other bacterial infection. 5.8 million people were newly diagnosed with TB in 2020. In the same year 1.3 million HIV negative and 214,000 HIV positive people died from TB.
Current treatment regimens are based on lengthy oral and parenteral dosage regimens with medications associated with many adverse effects which leads to poor patient adherence and the significant rise of multi drug resistance TB strains (MDR-TB). So, there is unmet clinical need to develop new treatment strategies to overcome MDR-TB and improve the treatment dosing regimen. An adjunctive host-directed therapy (HDT) could address these issues. HDTs act on the host instead of the bacteria, by boosting the host immune response, to augment the beneficial features of fighting the bacteria and reduce tissue damage. Administration of TB drugs locally via the pulmonary route to achieve high concentrations at the site of infection is important to enhance efficacy, target drugs towards the alveolar macrophages which are the niche for Mycobacterium tuberculosis (Mtb) and avoid systematic side effects, thereby providing better prognosis for TB patients, and reducing the incidence rate of MDR-TB.

One of the emerging HDTs for TB from our lab is All trans retinoic acid (ATRA) which is the active metabolite of vitamin A, currently a FDA approved drug for acne and acute promylocytic leukemia (Bahlool AZ et al, Curr Res Immunol, 2022). Drug repurposing of licensed medications such as ATRA is considered a streamlined approach for market access and reduces the industrial development costs and length of time to reach the patient. We have developed a formulation for targeted, host-directed TB treatment, using ATRA-loaded nanoparticles (NPs) that are suitable for nebulization. These nanoparticles have proven their in vitro efficacy against H37Ra Mtb and their safety in an in vitro airway epithelial cell model. This formulation has been successfully integrated with Aerogen Solo® vibrating mesh nebulizer (VMN) and the generated aerosol has favourable droplet size and aerodynamic properties for deep lung deposition (drafted manuscript). The nanoparticles have been successfully scaled up using the Ignite Nanoassembler® microfluidics system to enable more efficient clinical and commercial translation.

The project is a collaboration between academia, industry and clinical teams led by Prof. Sally-Ann Cryan at RCSI, the TB immunology group led by Prof. Joseph Keane and Dr. Mary O’Sullivan at St. James’ Hospital, Dublin and Dr. Ronan MacLoughlin at Aerogen Ltd, Galway. The project is now focusing on testing this inhalable TB therapy using state-of-the art animal models and performing advanced aerosol characterization to support the effective and timely clinical translation offering hope to millions of patients worldwide who are infected with TB annually.

Career Development Award Proposal

I look back a few years and feel very grateful for choosing this path, getting interested in science at a young age and craving to understand what is behind natural phenomena around me, sparking my curiosity and fuelled with love for science. Undertaking a PhD is never easy and throwing a pandemic on the top of this would make it more difficult. However, this made me more resilient and passionate to pursue my project focusing on respiratory diseases and respiratory drug delivery. The COVID-19 pandemic is significantly impacting Tuberculosis (TB) case-finding, management and access to treatment, leading to a drop in diagnosis and an increase in deaths compared with previous years. The pandemic has renewed the focus on the benefits of pulmonary drug delivery and drug repurposing as part of the global efforts to treat and tackle COVID-19. My ultimate goal is to build a strong academic healthcare-focused career and experience in the field of inhaled nanomedicines and therapeutic aerosol bioengineering for infectious diseases.

I completed my Pharmacy degree in 2016 with a research project focused on developing a silver nanoparticles-hydrogen peroxide based system to treat multi drug resistant infections (PLoS One. 2019. PMID: 31393906). In 2017, I got an Erasmus+ scholarship to do my Master’s degree. I was accepted into Erasmus Mundus Joint Master’s degree in Nanomedicine for drug delivery (NANOMED EMJMD) which is a mobility joint program between four universities; University of Paris Cite, University of Angers in France, University of Pavia in Italy and University of Patras in Greece. This diverse scientific and multicultural travel experience has provided me with many scientific and life skills that helped me grow in the academic field, learning to work with multiple research groups within multiple labs with different cultures and a unique multi-cultural travel experience that sharpened my personality and flexibility. During my Masters, I did a three months’ internship in MiNT research lab in Angers, working on a pre-clinical evaluation of a nanomedicine formulation for ovarian cancer in collaboration with a start-up company and Institute Curie. At the end of my second year, I completed my Master’s thesis at Queen’s University Belfast, UK, working on engineering targeted nanomedicines for advanced prostate cancer.

In 2019, I was accepted into the StAR (Strategic academic recruitment) PhD program at the Royal College of Surgeons in Ireland (RCSI), and this is when destiny took me into a whole new level. I was able in the first year to do 3 lab rotations on 3 different projects on tissue engineering, cancer bioinformatics and respiratory drug delivery. Then, I chose to develop and defend my PhD proposal on developing inhalable host directed immunotherapy for tuberculosis. During my PhD, I am developing an adjunctive inhaled ATRA-Loaded polymeric nanoparticles as host directed immunotherapy for TB to overcome the issue of multidrug resistance and improving the treatment regimen.

We have developed ATRA loaded poly-lactic-co-glycolic acid (PLGA) loaded nanoparticles at RCSI and proved their safety and the efficacy in an in vitro infection model of TB at the Trinity Translational Medicine Institute, St. James’ Hospital (Dublin). In collaboration with Aerogen, I have successfully integrated these ATRA-nanoparticles with the Aerogen Solo® vibrating mesh nebulizer and characterized the aerodynamic characteristics of the aerosol using laser diffraction and cascade impaction and assessed the delivered dose in simulated adult breathing pattern using a breathing simulator (drafted paper). Besides research, academic teaching and student supervision is part of my academic PhD life at RCSI, I’m enjoying supervising undergraduate Pharmacy students in their research projects and delivering practical pharmaceutics lab sessions.

We are currently moving on with this project to in vivo studies, in collaboration with Dr. Brian Robertson at School of Medicine at Imperial College London. Dr. Robertson’s lab has established a murine infection model of tuberculosis and we are hoping to test our formulation in vivo in this model to determine the in vivo efficacy and safety of our targeted delivery approach for ATRA as an adjunct treatment for Tuberculosis. During this part of my PhD, I will learn about the Mycobacterium tuberculosis murine infection model, and the delivery of the ATRA-nanoparticles to the lungs. We will monitor the bacterial burden and pathology in the lungs to assess efficacy of treatments compared to untreated controls and collect lung and Bronchoalveolar lavage (BALs) samples for further analysis of the effect on the immune cell population and cytokine profile. Lung tissue samples will be examined by a veterinary pathologist to assess the safety of the formulation. This part of my project will provide in vivo data to complement and extend my current studies and give me experience of working with specialized TB animal models, biological samples and working with class 3 biosafety animal facilities. In addition, the generated nanoparticle-loaded aerosols will be further characterized in simulated breathing adult and paediatric patterns with manikin head models for more clinically relevant characterization with our collaborators in Aerogen. This will allow me to gain a new set of skills and techniques that are not available for me to learn at my university and will allow me to bring it back to my research group, bridging the gap of experience that we need for the project.

In order to achieve my goal, a broad range of interdisciplinary knowledge and hands on experience will be required and the progress of this work is highly dependent on financial and technical support. The DDL career development grant would provide me with the support to strengthen the interdisciplinary collaboration between two different institutions in two different countries and enable me to expand my professional network. This grant if funded will support;
• My development of additional technical skills in the pre-clinical in vivo assessment of inhaled medicines and advanced aerosol characterization methods
• The pre-clinical assessment of our novel nanomedicine targeting TB in order to generate comprehensive data on the pre-clinical efficacy and safety of ATRA-nanoparticles with a view to applying for further funding to support clinical development and/or commercialisation with our clinical and industrial collaborators
• The presentation of project outcomes at international drug delivery, aerosol, and TB related conferences including DDL conference, Controlled Release Society (CRS), UK-Ireland Controlled Release Society local chapter (UKICRS), European Foundation of Clinical Nanomedicine (CLINAM) and Keystone TB, to gain valuable presentation and communication skills and experience with peers worldwide
• This grant will also enable me to engage with a group of outstanding infectious disease researchers in Imperial College London and thereby expand my professional network. It will give me the opportunity to get the experience of collaborating internationally across campuses and communicating my science to a scientific audience outside my field.

As an international student, I’m hoping to be able to bring the new skillset that I learn during my training back to my home country to do my own research and train new generations in my country on respiratory drug delivery research which is a field that we lack skilled expertise in. I believe that this grant will not only benefit me personally, but will indirectly benefit many people globally with the transferable skills that I will gain and teach to peers and younger generations.

This award will help the clinical translation of my project which could potentially save millions of patients worldwide who are infected with TB annually. It will allow me to build strong transferable interdisciplinary knowledge, skills, techniques and professional experience which will help me bridge to a strong career path in the field of respiratory drug delivery and help me to grow as a leader in the field.