Mohammad Momin

In Vitro Evaluation and Validation of a Novel Dry Powder Delivery Device Developed for Preclinical Pulmonary Administration in Mice.

Preclinical evaluation of inhaled therapeutics in animal models, particularly mice, is crucial for assessing pharmacokinetics, biodistribution, safety, and efficacy before clinical translation. Mice are widely used due to their genetic flexibility, low cost, and availability of disease models. Despite the dominance of dry powder inhalers (DPIs) in human respiratory drug delivery, accurate and reproducible delivery of dry powder formulations to mice lungs remains a significant technical challenge due to their small tidal volumes and the lack of appropriately scaled devices. The PennCentury DP-4M insufflator, widely used in preclinical studies, suffers from limitations such as manual actuation, poor powder de-aggregation, and operator variability—factors that result in inconsistent lung deposition. Moreover, this device is no longer commercially available. While alternatives like Aptar’s Powder Administration Device for Animals (PADA) exist, and exposure chamber systems like Scireq InExpose and Biaera AeroMP are used, these are either expensive, imprecise for powder delivery, or not optimized for individual dosing in mice. Such limitations contribute to variable dosing, low deposition efficiency, and hinder accurate pharmacokinetic and efficacy assessments, reducing reproducibility and translational value. To address these limitations, our group has recently engineered a novel, handheld dry powder delivery device specifically designed for precise pulmonary administration in mice. However, to establish this device as a viable tool for preclinical research, rigorous in vitro characterization and validation is essential.

This study aims to evaluate the in vitro performance of the newly developed dry powder delivery device across various powder formulations and compare it’s performance with a commercially available device. We hypothesize that the newly developed dry powder delivery device can deliver consistent and respirable particle sizes (1–5 µm) with minimal dose variability across multiple formulations, thereby providing a viable platform for murine inhalation studies.

The in vitro characterization involves particle size distribution of aerosol emitted from the device using Spraytec for a range of formulations; assessing dose uniformity and reproducibility across repeated actuations; comparing emitted dose and aerosol particle size across excipient and formulation types (e.g., micronized drugs, drug-lactose blends, spray-dried powder formulations). The validation involves the comparison of the performance of the novel device against the existing device (e.g. DP-4M). This successful evaluation of the device will provide foundational evidence of device functionality and formulation compatibility. The data generated will also support future in vivo studies. Overall, this work will significantly advance preclinical inhalation research by addressing a critical technological gap.

My goal is to become an independent academic investigator in the field of pharmaceutical sciences and a leader in respiratory drug delivery research with an aim to reduce the existing gap for successful translation of dry powder formulations from bench to bedside. With this interest, I did a Ph.D. on the development of a formulation platform of dry powder inhaler to improve the delivery efficiency of hygroscopic drug(s) to the lungs. As a Postdoctoral Research Fellow (Feb 2019-Jun 2023 in Prof. Michael Hindle’s lab at Virginia Commonwealth University, VCU) and Research Assistant Professor, my current position since Jul 2023 in the same lab at VCU, my current research focuses on the development and evaluation of surfactant dry powder formulations and devices for efficient delivery of aerosol formulations to infants and adults using the excipient enhanced growth (EEG) approach. Continuing my progress towards my career goal will require additional training in improving my research skills, writing grant applications, and collaborations with multidisciplinary research teams. The proposed project directly aligns with my career aspirations by allowing me to advance my knowledge and technical skills in addressing a critical technological gap to advance preclinical inhalation research. Also, this project will fill a critical methodological gap in inhalation research, improve translational relevance of preclinical studies, and accelerate the development of novel inhaled therapeutics. The extensive training in research methods and co-supervision skills that I received while earning a Ph.D. and postdoctoral training has provided the necessary foundation for me to be able to lead the proposed research project and advance my development as an independent investigator. The success of this project will build my confidence in developing my own research ideas and securing more grants from federal and industry/private grant bodies particularly from the National Institutes of Health (NIH), and Food and Drug Administration (FDA) to reach my career goal as an academic investigator. Along with the strong translational potential of this project, which may position me to contribute to future clinical innovations, the presentation of this work at inhalation research conferences such as Drug Delivery to the Lungs, Respiratory Drug Delivery and International Society for Aerosols in Medicine (ISAM) would expand my scientific network and collaborations with multidisciplinary research teams. In conclusion, the DDL Career Development Grant will be a catalyst for achieving my career ambitions by providing the necessary resources, exposure, and skill development to conduct innovative research in developing preclinical drug delivery devices.