Systemic and brain delivery of antidiabetic peptides through nasal administration using cell-penetrating peptides

Abstract

The intranasal route has emerged as a promising strategy that can direct delivery of drugs into the systemic circulation because the high-vascularized nasal cavity, among other advantages, avoids the hepatic first-pass metabolism. The nose-to-brain pathway provides a non-invasive alternative to other routes for the delivery of macromolecular therapeutics. A great variety of methodologies has been developed to enhance the efficiency of transepithelial translocation of macromolecules. Among these, the use of cell-penetrating peptides (CPPs), short protein transduction domains (PTDs) that facilitate the intracellular transport of various bioactive molecules, has become an area of extensive research in the intranasal delivery of peptides and proteins either to systemic or to brain compartments. Some CPPs have been applied for the delivery of peptide antidiabetics, including insulin and exendin-4, for treating diabetes and Alzheimer’s disease. This review highlights the current status of CPP-driven intranasal delivery of peptide drugs and its potential applicability as a universal vehicle in the nasal drug delivery.

Cell-Penetrating Peptides-Mediated Therapeutic Agents Delivery into the Central Nervous System

“…56−58 Furthermore, previous studies have provided evidence to support the notion that CPPs exhibit the ability to enhance the transportation of various molecules, such as biomolecules and nanoparticles, across the BBB, thereby improving CNS therapeutic efficacy. 55,59 In this section, we examined the principles, methods, and applications of CPPs as therapeutic agents and carriers for delivering biological macromolecules and nanoparticles across the BBB into the CNS.…”

Antimicrobial Peptides and Cell-Penetrating Peptides: Non-Antibiotic Membrane-Targeting Strategies Against Bacterial Infections

“… 85 Some CPPs have been applied for the delivery of peptide antidiabetics, including insulin and exendin-4, for the treatment of diabetes and Alzheimer’s disease. 86 …”

“…85 the delivery of peptide antidiabetics, including insulin and exendin-4, for the treatment of diabetes and Alzheimer's disease. 86 Few CPP-linked medications have been approved for topical and systemic administration in the clinic, although various CPP-based treatments have entered preclinical and clinical studies and have proven to be an effective delivery route for therapeutic compounds. To date, no CPP or CPP-conjugated drug has been approved by the US Food and Drug Administration (FDA) due to various negative characteristics, such as problems with toxicity, endosomal entrapment, immunogenicity, and in vivo stability issues.…”

Intranasal Delivery of Anti-Apoptotic siRNA Complexed with Fas-Signaling Blocking Peptides Attenuates Cellular Apoptosis in Brain Ischemia

“…Although various approaches, such as glucose transporters or receptor-mediated delivery through transferrin receptors, insulin receptors, leptin receptors, or acetylcholine receptors [ 23 , 24 , 25 , 26 , 27 , 28 , 29 ] have been explored, they face limitations in achieving effective drug delivery [ 30 , 31 , 32 ]. In response to challenges posed by the BBB, intranasal (IN) drug delivery has emerged as a promising and versatile approach, offering a direct and efficient pathway for administering various therapeutic agents [ 33 , 34 ]. This approach bypasses the BBB through the utilization of olfactory and trigeminal nerves and cerebrospinal fluid (CSF) as channels from the nasal cavity to the central nervous systems (CNS) and addresses the limitation associated with traditional routes such as oral or parenteral administration [ 35 ].…”