Investigation of the Transport Pathways Associated with Enhanced Brain Delivery of Peptide Drugs by Intranasal Coadministration with Penetratin

We previously found that coadministering peptides and proteins with the cell-penetrating peptide L-penetratin intranasally significantly increased transport to the brain and enhanced pharmacological effects. The present study aimed to clarify the mechanisms of nose-to-brain drug delivery enhancement by L-penetratin coadministration. First, we compared the concentrations of Exendin-4 in plasma and brain after intranasal and subcutaneous administration and suggested that coadministration with L-penetratin facilitated the direct nose-to-brain transport of Exendin-4. Second, we demonstrated that L-penetratin did not stimulate the transport of Cy7-labeled Exendin-4 and insulin through the trigeminal nerves but shifted their distribution to the olfactory mucosal pathway. Third, we investigated the distribution of insulin into the deeper regions of the brain after delivery via the olfactory pathway and suggested that insulin had entered the olfactory bulb, bottom part of the brain, and perivascular space through the cerebrospinal fluid and had diffused throughout the brain. We further demonstrated that intranasally delivered insulin with L-penetratin specifically accumulated on the hippocampus neuronal cells. Thus, this study suggested that administrating peptide drugs intranasally with L-penetratin allows direct transport to the olfactory bulb, bottom part of the brain, and perivascular space of the cerebral artery. This technique also potentially allows targeting of specific brain areas.

Patent Insight into the Development of Therapeutic Strategies against Coronaviruses

Coronaviruses are a group of RNA viruses, which cause diseases in humans. The emergence of COVID-19, has caused a global pandemic. It is focused on developing an effective therapeutic strategy against COVID-19. To better understand the development and evolution of therapeutic strategies against coronaviruses, we conducted US granted patents analysis. The results showed vaccines played a leading role in therapies against coronaviruses. Both attenuated vaccines and recombinant genetic vaccines were very important approaches in vaccine development against coronaviruses. It is not a rapid approach to develop peptide drugs against COVID-19 or future novel coronaviruses. The study was the first one to show the development and evolution in therapeutic strategies against coronaviruses based on patent insight. The present study provides a new insight into the development of therapeutic strategies against coronaviruses.

Ingestive Peptides – An Emerging Tool for Diagnostics and Therapeutics: A Review

Peptides are relatively safe, well tolerated, highly selective and efficacious. Consequently, in recent years, peptides have acquired an increased interest as therapeutics in pharmaceutical research and development. In clinical trials, about 140 peptide therapeutics are currently being tested. In medicine and biotechnology, peptides have acquired a broad range of applications. More than 7000 peptides in nature have been recognized, and these peptides also have critical roles including actions as hormones, growth factors, neurotransmitters, ion channel ligands, or anti-infectives. Peptides are often excellent biomarkers and can be used for diagnostic purposes. Metabolic diseases and oncology are the major disease areas nowadays driving the clinical use of peptide drugs. We think that the future peptide drugs development will be a new tool for the several pathologies amelioration.

Towards the Development of Orally Available Peptide Therapeutics

Peptides have a number of attractive properties that make them an interesting modality for drug development, including their ability to bind challenging targets, their high target specificity, and their non-toxic metabolic products. However, a major limitation of peptides as drugs is their typically poor oral availability, hindering their convenient and flexible application as pills. Of the more than 60 approved peptide drugs, the large majority is not orally applicable. The oral delivery of peptides is hampered by their metabolic instability and/or limited intestinal uptake. In this article, we review the barriers peptides need to overcome after their oral administration to reach disease targets, we highlight two recent successes of pharma companies in developing orally applicable peptide drugs, and we discuss efforts of our laboratory towards the generation of bioavailable cyclic peptides.

Peptidomimetics and Peptide-Based Blockbuster Drugs

: Amino acids (AAs) play an important role in modern health industry. AAs’ residues are frequently found in the structures of small-molecule modern pharmaceuticals, while peptidomimetics and peptide-based drugs are entirely derived from AAs. The goal of this review article is to highlight that, currently, AAs serve as key structural features in numerous successful pharmaceuticals; they are the so-called blockbuster drugs. In this work, we provide a detailed profile of 5 peptidomimetics and 4 peptide drugs. For each compound, we describe the spectrum of biological activity, medicinal chemistry discovery, and synthetic preparation.