Oesophageal tissue screening system for assessing the retention and mucosal absorption of biologics
摘要
Drug delivery to the oesophagus poses unique challenges, including rapid transit time due to gravity and the presence of a stratified squamous non-keratinized epithelium. Here, to rapidly identify formulations of excipients for enhanced drug delivery to the oesophagus, we developed an oesophageal tissue screening system consisting of specialized custom plates, to incorporate gravity effects, and excised oesophageal mucosa tissues. Using the screening system, we built an excipient library identifying the most effective non-toxic permeation enhancers and selected the formulation that could prolong the retention on the oesophageal mucosa. We identified an absorption enhancer that resulted in a 876-fold increase in the oesophageal transport of a model drug (4 kDa) in pig tissue. We validated this formulation in human oesophageal tissue and in vivo in pigs with the model drug and infliximab (149 kDa), demonstrating enhanced permeability. We characterized the mechanism of the approach, noting its capacity for enhanced delivery without causing cellular disruption of the oesophageal tissue. The oesophageal tissue screening system shows promise for high-throughput screening of effective oesophageal drug delivery systems.