Rational design of CPP-based drug delivery systems: considerations from pharmacokinetics

Area of Science:

• Biotechnology
• Drug Delivery
• Molecular Biology

Background:

• Cellular internalization of therapeutics is hindered by the cell membrane, especially for high molecular weight drugs.
• Cell-penetrating peptides (CPPs) are effective carriers for delivering large molecules like proteins, siRNA, and nanoparticles into cells.
• Current CPP-based therapies face challenges due to poor pharmacokinetics, including rapid renal clearance and lack of specificity.

Purpose of the Study:

• To review the current knowledge on CPPs, focusing on strategies to overcome pharmacokinetic limitations.
• To highlight advancements in CPP design for improved targeting and reduced clearance.
• To explore novel delivery routes that expand the clinical applicability of CPPs.

Main Methods:

• Literature review of current research on cell-penetrating peptides.
• Analysis of strategies for enhancing CPP pharmacokinetics and cellular uptake.
• Examination of emerging CPP applications and delivery pathways.

Main Results:

• CPPs offer a versatile platform for intracellular drug delivery.
• Rational design approaches, including targeting sequences and molecular weight adjustments, can improve CPP performance.
• Activatable CPPs and alternative absorption pathways (nasal, pulmonary, transdermal) show promise for clinical translation.

Conclusions:

• Overcoming pharmacokinetic limitations and clarifying internalization pathways are key to realizing the full potential of CPPs.
• Strategic design modifications and exploration of new delivery routes are essential for advancing CPP-based therapeutics.
• CPPs hold significant promise for future clinical applications in targeted intracellular drug delivery.