This Career award by the Biomaterials program in the Division of Materials Research to Purdue University is to study mucus materials with abnormal rheological properties that significantly interfere with effective transport of nanoparticles. This project is to develop a new drug delivery strategy utilizing osmotic agents to overcome the mucus barrier. The underlying hypothesis of this project is that osmolytic agents will induce local influx of water in mucus materials to generate two favorable effects for nanoparticle diffusion: (1) induce collapse of neighboring biopolymer network, thereby increasing the spacing in the polymer mesh; and (2) decrease the viscosity of liquid in microscopic domains within the network. This project will use microscopic techniques to compare various osmolytic agents for the effect on transmucosal nanoparticle diffusion, design formulations that integrate effective osmolytic agents and nanoparticle, and evaluate the effectiveness of the osmolyte formulations using a chronic lung infection model. The outcome of this study will enhance understanding of mucus materials as a physiological barrier to drug delivery and would provide a reasonable strategy to improve treatment of diseases suffering from the mucus barrier. The proposed research will contribute to the education of next generation materials scientists, by training students in cutting-edge experimental techniques and working knowledge in the related fields. In addition, the PI will create an undergraduate class that develops training materials for K-12 students in collaboration with the Purdue Engineering Projects in Community Service.
Delivering nanoparticulate therapeutics to tissues covered by abnormally thickened mucus is challenging because the mucus materials behave as a physical and chemical trap of particles and thus interfere with effective therapy in cystic fibrosis, chronic lung diseases or other related ones. The proposed project will introduce osmolytic agents in the formulation to enhance the nanoparticles penetration into the mucus materials. The underlying hypothesis is that an effective osmolytic agent will cause influx of water into the mucus and, thus, create pores that are easier for nanoparticles to travel through. This project will compare various osmotic agents for the ability to influence mucus, design and produce pharmaceutical formulations combining nanoparticles and the osmotic agents, and evaluate the effectiveness of this strategy using an animal model with chronic lung infection. The outcome of this study will enhance understanding of mucus as a physiological barrier to drug delivery, and would provide a reasonable strategy to improve treatment of diseases suffering from the mucus barrier. The proposed research will contribute to the education of next generation biomaterial scientists and engineers, by training students in cutting-edge experimental techniques and providing them with hand-on experiences. In collaboration with the Purdue Engineering Projects in Community Service, the project will create an educational program that engages K-12 and undergraduate students to stimulate public interest in science and technology.
