Nano-Inspired Technologies for Peptide Delivery

Abstract

Nano-inspired technologies offer unique opportunities to treat numerous diseases by using therapeutic peptides. Therapeutic peptides have attractive pharmacological profiles and can be manufactured at relatively low costs. The major advantages of using a nanodelivery approach comprises significantly lower required dosages compared to systemic delivery, and thus reduced toxicity and immunogenicity. The combination of therapeutic peptides with delivery peptides and nanoparticles or small molecule drugs offers systemic treatment approaches, instead of aiming for single biological targets or pathways. This review article discusses exemplary state-of-the-art nanosized delivery systems for therapeutic peptides and antibodies, as well as their biochemical and biophysical foundations and emphasizes still remaining challenges. The competition between using different nanoplatforms, such as liposome-, hydrogel-, polymer-, silica nanosphere-, or nanosponge-based delivery systems is still “on” and no clear frontrunner has emerged to date.

Development of a Gene Delivery System Composed of a Cell-Penetrating Peptide and a Nontoxic Polymer

“…Proteins, peptides, oligonucleotides, and polynucleotides are being investigated as potential therapeutic agents. − These agents are usually highly specific and easier to advance to clinical trials than chemical drugs. Cell-penetrating peptides (CPPs) hold a lot of promise, such as ease of synthesis, low cytotoxicity, straightforward redesign of amino acid sequences, and incorporation of non-natural amino acids .…”

“…Proteins, peptides, oligonucleotides, and polynucleotides are being investigated as potential therapeutic agents. − These agents are usually highly specific and easier to advance to clinical trials than chemical drugs. Cell-penetrating peptides (CPPs) hold a lot of promise, such as ease of synthesis, low cytotoxicity, straightforward redesign of amino acid sequences, and incorporation of non-natural amino acids . However, a major drawback of CPPs is their low membrane permeability due to hydrophilic properties, which becomes a major challenge when it comes to cross the blood–brain barrier and penetrate tissues throughout the body .…”

“…However, a major drawback of CPPs is their low membrane permeability due to hydrophilic properties, which becomes a major challenge when it comes to cross the blood–brain barrier and penetrate tissues throughout the body . Opportunities to overcome these challenges became possible after identifying CPPs with translocation capacities. ,− In 2010, Eiriksdottir et al analyzed the structure of 10 well-known CPPs and their abilities to interact with lipid layers. They demonstrated that peptides that formed helix groups were able to insert spontaneously into lipid monolayers, which suggests spontaneous insertion into biological membranes .…”

“…They demonstrated that peptides that formed helix groups were able to insert spontaneously into lipid monolayers, which suggests spontaneous insertion into biological membranes . Most CPPs consist of cationic domains, a feature that was considered to be essential for cellular penetrations. , However, recent studies have demonstrated that amphiphilicity seemed to play a bigger role in cellular entry than positively charged domains. ,, It is important to mention that a single point mutation and/or deletion of a single amino acid in a peptide chain can alter the amphipathic domain and weaken cellular uptake properties.…”

“…A major challenge faced when using peptides as drug delivery systems is their lack of specificity. It has also been suggested that CPP internalization is limited to only a few cell types because requirement-specific lipid compositions are required for peptide penetration. , For this reason, the idea of using a secondary nanocarrier has been introduced to overcome these challenges …”