The outer surface of organs and blood vessels throughout the human body and inner cavities of various internal organs are fenced by epithelial tissues responsible for the biological barriers. For example, the epidermis, the outermost layer of the skin, and the intestinal epithelium that lines the gastrointestinal tract provide barriers to the skin and the intestine, respectively. The role of these epithelial barriers is to not only prevent the entry of foreign entities into the organ but to also control the transport of molecules across the barrier. These barriers are selective to molecules having a specific size and chemical interactions. Hence, understanding the body’s biological barriers thus represents a key step for creating better drug delivery systems. To deliver therapeutics into the body , biological barriers must be reversibly breached in controlled ways such that molecules can pass through them. Several strategies such as prodrugs, nanomaterials, polymers, mucoadhesive devices and permeation enhancers are being explored, and they are at the various stages of the drug development cycle (pre-clinical to clinical trials). The ionic liquids are a new class of permeation enhancers currently being explored for delivering high molecular weight therapeutics across the skin and oral routes. However, there is little understanding of how these molecules interact and breach the skin and intestinal barrier. In this project, we are using molecular dynamics simulations to develop and improve all-atom and coarse-grained models for biological barriers such as the skin and intestine. These models are used to understand the permeation of molecules across these barriers. Advanced free energy methods such as metadynamics and umbrella sampling are used to calculate the permeation of molecules across different membrane models to represent the skin and intestine. Further, the interaction of these permeation enhancers is being explored to understand their permeation mechanism, which would help in exploring a new class of permeation enhancers.
