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Pulkit KhatriPulkit Khatri is currently in his second year of studies as a Ph.D. student of Industrial Pharmacy in the Department of Pharmaceutical Sciences at St. John’s University, mentored by Associate Professor Jun Shao.

Advancements in the development of recombinant proteins and peptides with therapeutic potential have dramatically changed the biotechnology and pharmaceutical market, but the requirements of parenteral delivery limits their usage. Therefore, there is great need for a noninvasive protein and peptide drug delivery system.

Oral administration is the most convenient route for patients. For protein and peptide delivery, however, this type of delivery has been a great challenge because of extensive degradation and limited absorption. To overcome these hurdles, several strategies have been developed and have achieved limited success. Some studies have shown that adequate absorption can be achieved if there is enough protein present on the absorption surface or if the enzyme degradation is inhibited. Therefore, a system that can continuously and directly release the protein on the absorption surface will increase the bioavailability. In addition, this will also minimize the protein exposure to the harsh intestinal environment.

One such system is the genetically engineered normal flora, due to their compatibility with the host’s immune system, natural tendency to adhere tightly to the epithelial surface, controllable persistence in the gut, and ability to be safely administered orally. Through recombinant DNA technology, normal flora can be made to secrete many protein and peptide drugs. Therefore, normal flora is emerging as potential candidates for the production of many heterologous proteins.

Previous studies in our laboratory have demonstrated the feasibility of this approach. I believe the selection of a strain with desired adhesive capability, use of pro-peptide design to increase the yield and secretion of the mature protein, and use of protein conjugates and/or amino acid modifications can further improve the oral absorption, allowing normal flora to constitute an efficient drug delivery system.

Although great progress has been made in this area, there are still some limitations to overcome. With advances in genetic modifications of normal flora, scientists may be able to overcome challenges for the oral delivery of certain protein and peptide drugs.

What other drug delivery pathways do you think hold promise for protein and peptide drugs?