Cyclic Peptides: Design, Characterization, Self-Assembly, and Applications as Nano Drug Delivery Systems

Abstract

Over the past two decades, drug delivery systems have become a subject of major interest in the pharmaceutical industry for the treatment of different diseases, such as cancer, viral infections, and genetic disorders. A wide range of compounds show high binding affinity and great potential in in vitro non-cellular assays through direct interacting with molecular targets. However, many compounds show low potency in cell-based assays due to their limited delivery across the cell membrane. The physicochemical properties of several compounds, such as size, poor water solubility, hydrophobic nature, and negative charge, limit their cellular uptake significantly. Thus, there is an urgent need in design and synthesis of novel molecular transporters for efficient delivery of effective compounds to cellular targets. The recent growth of nanotechnology products will expand the current resources of therapeutics for the pharmaceutical industry in the next few years. The use of nanotechnology in drug delivery is widely expected to change the future of the pharmaceutical and biotechnology industries. The application of nanotechnology in drug delivery has led to the discovery of nano Drug Delivery Systems (nano-DDS). Nanocarriers exhibit unique properties and take advantage of specific physiochemical behavior of nanoparticles. Properties such as, magnetism, conductivity, melting and boiling points, and chemical and biological reactivity become different at nano scale due to the quantum mechanical behavior of extremely small structures at molecular dimensions. Furthermore, nanoparticles behave differently since they take advantage of extraordinary high surface area to mass ratio, leading to increased surface interactions and distinct biological performance. Nanoparticles have the potential to be manipulated through changing their size, electronic, and hydrophobic nature. Employing nano-sized carriers offer several advantages, including enhanced intracellular delivery of poorly water-soluble drugs, targeted delivery, transporting relatively large biologically important molecules across the cell membrane, delivery of a combination of drugs to overcome drug resistance, and transporting drugs through challenging epithelial and endothelial barriers. Thus, design and development of nano-sized pharmaceutical carriers has become attractive for chemists, biologists, and physicists. Functionalized Nano-DDS are designed to deliver and release cargo drugs intracellularly more efficiently than the currently available systems, leading to the enhanced drug tissue bioavailability and eventually therapeutics efficacy. Among all nano-DDS, Cell-Penetrating Peptide (CPP)-mediated intracellular DDS has been widely used for the enhanced delivery of water insoluble drugs, negatively charged molecules (e.g., DNA, siRNA, phosphopeptides), and proteins. However, the application of (CPP) mediated intracellular DDS in in vivo models has been challenging due to