Functional Modulation of Tight Junction to Enhance the Permeability of Biological Products (Biologics) in Biomembranes.

In recent years, biological products (biologics), including blood components, recombinant therapeutic proteins, antibodies, gene therapeutic materials, and so on, have been produced by biotechnology methods and other novel technologies. These products are essential therapeutic materials in progressive medicine. However, we often encounter the lower permeability of these biologics through biomembranes, due to their high molecular mass. In the last three decades, we have investigated drug delivery systems, including several enhancement methods for the permeability of biologics such as recombinant therapeutic proteins and viral vectors in epithelial cells. This review focuses the development of novel delivery systems for biologics in rectal and nasal administration, and includes an interesting observation of modulators of the tight junction (TJ) function. From cellular biology perspective, the interaction between permeability enhancing materials and targeted molecules in the TJ of epithelial cells was investigated. We elucidated that a TJ modulator will interact with a major constituent protein, for instance claudins, in playing an essential role in the tissue-specific barrier function of the TJ. Furthermore, useful enhancement of gene transfer in cells (for instance, in Caco-2 cells) was found in the combination of an adenovirus vector and capric acid sodium salt (C10), a TJ modulator.