Chief Scientific Officer, Upperton Pharma Solutions
DDL has always been the place where scientists bring the brightest and newest ideas in the fast-moving nasal and pulmonary delivery arena and this year’s conference was no different. The conference opened on Day 1 with the EPAG workshop, a forum where European regulators and academic leaders discussed recent shifts affecting orally inhaled and nasal drug product (the OINDPs). This regulatory discussion was hugely valuable for those in attendance and indeed, it set a benchmark for the remainder of the conference.
In the first scientific session a discussion took place on the integration of innovative AI and human relevant models to transform and accelerate respiratory drug development. Whilst EPAG urged caution and completeness, this talk championed intelligent velocity: using AI to predict translational risk and streamline preclinical decision making with models that better predict human biology. The contrast between this opening session and the previous EPAG workshop was quite interesting, and both led to the same question “To what extent can we compress time without compromising quality”? Perhaps the overall conclusion was that AI can support with pattern recognition across multimodal datasets and faster iteration cycles, whilst the regulatory frame insists that acceleration must be coupled to accountability. Taken together, the message for developers is not “choose one” but “use AI innovatively to speed up the development process.”
The first day continued with an evaluation of human primary nasal cells. The discussion examined human primary nasal epithelial cells grown at the air–liquid interface that are designed to reproduce the functional architecture of the nasal mucosa. The conclusion emerging from this study was that different donors respond differently to bacterial stimulation. Therefore, when grown at the air-liquid interface, the biobank of well-characterised epithelial cell samples helps to ensure more consistent experiments, better reproducibility and an improved translation of lab findings to real clinical use.
In nose-to-brain research, these models are now considered the gold standard for testing due to the level of primary cell variability. This variability reminds us that the unpredictability of human biology can have a significant impact on absorption, local tolerability, and efficacy in real time. The take-home message for teams building inhaled and nasal products is that robustness is achieved by designing a series of tests that can detect and interpret outliers, especially in early development, when changes are still inexpensive and reversible.
Formulation science then stepped into the foreground with an examination of apramycin as an inhaled antibiotic and the impact of formulation efforts on lung permeation using an ex vivo isolated, perfused, and ventilated rat lung model. This lecture provided a timely reminder to the audience that getting complex molecules to the right place at the right concentration for the right duration is a difficult challenge to development scientists. Particle engineering, excipient selection, and aerodynamic performance are clearly some of the key levers that tune regional deposition, mucosal interaction, and ultimately therapeutic index. If any of these key variables is underdeveloped, the system underperforms. Apramycin’s journey, therefore, acts as a case study in how theoretical promise must traverse very physical gates before a therapy can claim relevance in the clinic.
When the conference later pivoted to “the airways and beyond,” focus switched to the nose-to-brain frontier in more detail. The lecture described this pathway as a narrow shortcut to the CNS, emphasising anatomical constraints, deposition geometry, and mucosal clearance that make success possible but fragile. Work on transport and intracellular uptake across nasal epithelial and neuroblastoma cells highlighted barriers, endocytotic routes, and celltype specificity that turn the shortcut into a series of gates.
"DDL 2025’s lectures were once again insightful in underlining the challenges and opportunities for innovators in both the pulmonary and nasal drug delivery sectors of the pharmaceutical industry."
A further presentation on in situ hydrogels for nasal delivery of antibiotics demonstrated how rheology and residence time interact with airflow and anatomy to maximise drug delivery.
The final presentation focussed on the potential for nanoagglomerate cholecalciferol to achieve nose-to-brain delivery as a first aid therapy for ischemic stroke. These talks reveal a continued interest in the nose-to-brain route. However, challenges remain, with nasal anatomy, the challenge of paracellular transport, drug formulation and device performance creating some of the key barriers for successful utilisation in an emergency setting.
In summary, DDL 2025’s lectures were once again insightful in underlining the challenges and opportunities for innovators in both the pulmonary and nasal drug delivery sectors of the pharmaceutical industry. The directive is simple yet demanding: build programmes that respect the regulatory guardrails, leverage intelligent acceleration, anticipate biological diversity, choose the most relevant models and design formulations that have the best chances of achieving successful delivery.