Peptide-based delivery systems: selected insights into cell-penetrating peptides
File(s)
Published version
Author(s)
Adam, Hussan
Abdollahi, Sara
Al Musaimi, Othman
Type
Journal Article
Abstract
The blood–brain barrier (BBB) is a highly selective biological interface that regulates molecular transport between the bloodstream and the central nervous system (CNS). Its primary function is to protect the brain from harmful substances while maintaining neural homeostasis. This regulatory capacity is attributed to its complex, multilayered structure, comprising nonfenestrated endothelial cells, astrocytic end-feet, pericytes, specialized transporters, and efflux pumps, along with dynamic mechanisms that adapt to physiological changes. Despite its essential protective role, the BBB presents a significant obstacle to the delivery of therapeutics targeting CNS disorders, limiting the ability of many drugs to reach their intended sites of action. Numerous invasive and noninvasive strategies have been explored to enhance CNS drug delivery; however, many are hindered by limitations such as low efficacy, poor specificity, and immunogenicity. Peptides, as endogenous short chains of amino acids, offer a promising alternative due to their high biocompatibility, ease of synthesis, and structural versatility. Their cationic charge facilitates interactions with negatively charged proteoglycans on cell surfaces, while their amphiphilic nature enhances membrane permeability, enabling efficient cellular uptake and translocation. These properties make peptide-based vectors particularly suitable for transporting diverse therapeutic cargoes across biological barriers. This review discusses the structural characteristics, origins, and classifications of peptide vectors, as well as the mechanisms underlying their cellular internalization. It further evaluates their advantages and current limitations in clinical applications, and highlights emerging strategies aimed at optimizing peptide-mediated delivery across the BBB.
Date Issued
2026-07-15
Date Acceptance
2026-05-20
Citation
ACS Chemical Neuroscience, 2026, 17, pp.2560-2576
ISSN
1948-7193
Publisher
American Chemical Society (ACS)
Start Page
2560
End Page
2576
Journal / Book Title
ACS Chemical Neuroscience
Volume
17
Copyright Statement
© 2026 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0.
License URL
Identifier
10.1021/acschemneuro.6c00266
Subjects
cell-penetrating peptides (CPPs)
blood−brain barrier delivery
peptide-mediated transport
intracellular drug delivery
CNS therapeutics
peptide-based nanomedicine
Publication Status
Published
Date Publish Online
2026-06-03