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Peptide and protein drug delivery to and into tumors: challenges and solutions
Vladimir P Torchilin1, Anatoly N Lukyanov
1Department of Pharmaceutical Sciences, Bouve College of Health Sciences, 312 Mugar Bldg. Northeastern University, 360 Huntington Ave, Boston, MA 02115, USA. v.torchilin@neu.edu
Abstract:
The potential of peptide and protein anticancer agents has yet to be realized owing to the many unresolved problems concerning their delivery to the site of a tumor and into tumor cells. However, our understanding of the mechanisms underlying the biological fate and biodistribution of protein and peptide drugs has advanced to the stage where methods that use or influence these mechanisms are now available. There are different approaches that can improve the stability, longevity and targeting of peptides and proteins in the body, such as their modification with various soluble polymers, incorporation into microparticular drug carriers, enhanced permeability and retention effect-based tumor targeting and the use of targeting moieties. Furthermore, new approaches to intracellular drug delivery, including the use of transduction proteins and peptides, are being developed. These advances promise the delivery of a new generation of anticancer drugs.
Insights
Peptide and protein anticancer drugs face delivery challenges. New methods enhance drug stability, targeting, and intracellular delivery for next-generation cancer therapies.
Area of Science:
- Biomedical Engineering
- Pharmacology
- Oncology
Background:
- Peptide and protein anticancer agents hold significant therapeutic promise but face substantial delivery hurdles.
- Realizing their full potential requires overcoming challenges in tumor site accumulation and intracellular penetration.
- Advances in understanding drug biodistribution and biological fate are paving the way for improved delivery strategies.
Purpose of the Study:
- To review current and emerging strategies for enhancing the delivery of peptide and protein anticancer agents.
- To highlight methods that improve drug stability, longevity, and tumor targeting.
- To discuss novel approaches for achieving intracellular drug delivery.
Main Methods:
- Modification of peptides and proteins with soluble polymers to improve stability and circulation time.
- Encapsulation of therapeutic peptides and proteins into microparticular drug carriers.
- Utilizing the enhanced permeability and retention (EPR) effect for passive tumor targeting.
- Employing specific targeting moieties to direct drugs to tumor cells.
- Developing intracellular delivery systems, including the use of transduction proteins and peptides.
Main Results:
- Various formulation and modification strategies can significantly enhance peptide and protein drug pharmacokinetics and tumor accumulation.
- Polymer conjugation, microencapsulation, and EPR-based targeting are effective in improving drug delivery.
- Novel intracellular delivery techniques show promise for overcoming cellular barriers.
- These combined approaches are crucial for the successful clinical translation of peptide and protein therapeutics.
Conclusions:
- Significant progress has been made in addressing the delivery challenges of peptide and protein anticancer agents.
- The development of advanced drug delivery systems is critical for unlocking the therapeutic potential of these biomacromolecules.
- These innovations are paving the way for a new generation of effective anticancer therapies.