Cell-Penetrating Peptides (CPPs)-Engineered PLGA Nanocarriers Advance Drug Delivery by Overcoming Cellular Barriers

Insufficient cellular membrane permeability remains a significant hurdle for effective pharmaceutical administration, limiting the intracellular delivery of many therapeutic agents. Traditional drug delivery methods often struggle to efficiently transport cargo across this natural barrier, reducing drug bioavailability and efficacy. Cell-penetrating peptides (CPPs) have emerged as powerful biological carriers, capable of traversing cell membranes and facilitating the internalization of conjugated therapeutic agents. Their ability to enhance cellular uptake makes them ideal candidates for improving nanoparticle (NP) delivery systems, particularly when combined with biodegradable polymers like PLGA (poly(lactic-co-glycolic acid)) to create next-generation drug delivery systems (DDS).

This comprehensive review synthesizes the current landscape of CPPs-functionalized PLGA-derived nanocarriers, exploring their development, mechanisms of action, and therapeutic applications. The authors systematically examined existing literature to summarize the state-of-the-art in CPPs/PLGA nanocarrier design and performance. They specifically addressed the various challenges encountered in their application and detailed optimization techniques aimed at improving their efficacy and safety. The review concludes by outlining future prospects and persistent challenges for CPPs/PLGA nanocarriers in advanced drug delivery systems.

The review highlights that CPPs are extensively recognized as effective biological carriers, significantly enhancing the cellular internalization of therapeutic agents by overcoming the cellular membrane's insufficient permeability. CPPs-assisted delivery systems, particularly those utilizing PLGA nanoparticles, have gained substantial attention due to their distinctive features, making them highly appealing for advanced drug delivery. These CPPs-conjugated PLGA NPs have demonstrated considerable promise as therapeutic agents across a wide spectrum of medical fields, showcasing their versatility and potential. The article systematically explores the current development, identifying key advancements in their design and functionalization. > The review underscores that CPPs-functionalized PLGA nanocarriers represent a cutting-edge approach to drug delivery, effectively addressing the critical challenge of intracellular transport for a diverse range of therapeutic molecules. Furthermore, the authors detail various optimization strategies that have been developed to enhance the performance, stability, and targeting specificity of these nanocarriers, alongside a thorough discussion of the remaining challenges that need to be overcome for widespread clinical translation.