S.S. Davis – författare

Recent years have seen enormous advances in the field of protein and peptide engineering and a greater understanding in the way in which biological response modifiers function in the body. It is now possible through the use of recombinant DNA techniques, or by solid phase protein synthesis, to produce significant quantities of a wide variety of regulatory agents that are therapeutically applicable. The list of these response modifiers expands almost daily to include interferons, macrophage activation factors, neuropeptides and agents that may have potential in cardiovascular disease, inflammation, contraception etc. Prospects to use some of these materials in medicine have reached the stage where products have either been approved by regulatory authorities or are the subject of applications as investigatory drugs or as new therapeutic agents. In some uses the pertinent agent will be administered on an acute basis in the form of a simple injection, as, for example, the use of a tissue plasminogen activator for the treatment of coronary infarct. In other cases regulatory proteins and peptides are indicated for chronic therapy and here they will need to be administered by an appropriate delivery system. Unfortunately, the research on delivery systems for peptides and proteins has not kept pace with the rapid progress in biotechnology and, consequently, there are presently few systems that are entirely appropriate for the administration of macromolecular drugs according to complex dosage regimens, (eg intermittent and pulsed therapy). Furthermore essential pharmacokinetic and pharmacodynamic data may be missing.

In recent years there have been rapid advances in the growth and differentiation of mammalian cells in culture. This has led to increasing use of such in vitro systems in a wide variety of studies on fundamental aspects of cell structure and function, including normal growth and metabolism, mechanisms of differentiation and oncogenesis, mechanisms of protein and membrane synthesis and cell polarity. Recent advances in our ability to grow cells, including human cells, on permeable supports, to generate confluent cellular barriers with the morphological polarity corresponding to their in vivo counterparts has greatly facilitated such studies. In particular these new techniques have led to an increasing interest in the use of cell and tissue culture systems as a means for examining the transport of drugs across epithelial and endothelial barriers. An obvious question is whether these new in vitro methodologies will provide convenient systems that can substitute for and replace animal models. Various research groups both in academia and in the pharmaceutical industry have been investigating these types of methodologies in order to develop convenient well characterized systems that can be used to examine basic aspects of transcellular transport and to evaluate the permeability of drug molecules and delivery systems. Of particular note is use of confluent cell layers to study the transport of large molecules such as peptides and proteins produced through recombinant DNA technology.