Related Experiment Video
Updated: Jul 21, 2025

Construction of Cyclic Cell-Penetrating Peptides for Enhanced Penetration of Biological Barriers
Published on: September 19, 2022
Cell-Penetrating Peptide-Based Delivery of Macromolecular Drugs: Development, Strategies, and Progress
Zhe Sun1, Jinhai Huang1, Zvi Fishelson2
1School of Life Sciences, Tianjin University, Tianjin 300072, China.
Abstract:
Cell-penetrating peptides (CPPs), developed for more than 30 years, are still being extensively studied due to their excellent delivery performance. Compared with other delivery vehicles, CPPs hold promise for delivering different types of drugs. Here, we review the development process of CPPs and summarize the composition and classification of the CPP-based delivery systems, cellular uptake mechanisms, influencing factors, and biological barriers. We also summarize the optimization routes of CPP-based macromolecular drug delivery from stability and targeting perspectives. Strategies for enhanced endosomal escape, which prolong its half-life in blood, improved targeting efficiency and stimuli-responsive design are comprehensively summarized for CPP-based macromolecule delivery. Finally, after concluding the clinical trials of CPP-based drug delivery systems, we extracted the necessary conditions for a successful CPP-based delivery system. This review provides the latest framework for the CPP-based delivery of macromolecular drugs and summarizes the optimized strategies to improve delivery efficiency.
Related Concept Videos
Cellular Membranes and Drug Transport
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.
Mechanisms of Drug Absorption: Paracellular, Transcellular, and Vesicular Transport
However, most drugs use the transcellular route, traversing directly through the cell membranes via two mechanisms: passive and active transport. Passive...
Drug Delivery: Overview
Enteral delivery involves administering drugs directly through swallowing, sublingual placement, or buccal application. Orally administered drugs predominantly navigate the...
Carrier-Mediated Transport
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Pore Transport and Ion-Pair Transport
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct...

