Innovative Engineering Methods Unlock New Potential for Crossing the Blood-Brain Barrier

A recent study in The Journal of Pharmacology and Experimental Therapeutics has unveiled new findings that pave the way for advanced drug delivery systems with the potential to target brain diseases more effectively. Cellular vesicles (CVs) have emerged as a promising alternative to conventional exosomes in transporting therapeutic agents across the impermeable fortress of the blood-brain barrier (BBB).

The groundbreaking research is situated at the intersection of cell engineering, nanotechnology, and pharmacology. The collaborative effort spearheaded by scientists from the Foundation for Research and Technology Hellas and the University of Patras, Greece, along with their international partners, presents a vital move forwards in biomedicine.

DOI: (https://doi.org/10.1124/jpet.119.257097)

Understanding Cellular Vesicles

Cellular vesicles are naturally occurring biological structures that shuttle proteins, lipids, and genetic material between cells. These vesicles have long intrigued scientists as potential delivery vehicles for drugs, particularly for conditions affecting the brain where treatment options are limited by the BBB—a highly selective membrane that guards the brain against foreign substances.

Existing research on exosomes, a type of cellular vesicle, has been a focus for potential therapeutic designs. However, exosomes present limitations in terms of scalability and potential immune responses. The recent study suggests that engineered CVs can overcome these issues.

Advancements in CV Production and Characterization

In this innovative research endeavor, CVs were prepared from human embryonic kidney 293 cells (HEK-293), C57BL/6 mouse B16F10 skin melanoma cells (B16F10), and immortalized human cerebral microvascular endothelial cells (hCMEC/D3) using liposome technology methods.

Key Findings

1. CVs exhibited sizes ranging between 135 and 285 nm.
2. Morphological assessment and proteomic analysis confirmed their biocompatibility and stability.

The Potential for Brain Targeting

What sets this study apart is the successful in vitro and in vivo exploration of the brain-targeting potential of the engineered CVs. Leveraging an hCMEC/D3 BBB model, the researchers evaluated the CVs’ ability to cross this highly restrictive barrier. Their investigation extended to in vivo studies, where the biodistribution of fluorescently labeled CVs was monitored, revealing significantly enhanced brain targeting.

The Future of Drug Delivery to the Brain

The implications of these findings are momentous, particularly for the treatment of neurodegenerative diseases, brain tumors, and other central nervous system disorders. By unlocking a new mechanism to bypass the BBB, CVs could revolutionize how treatments are delivered to the brain.

Next Steps and Considerations

Further research is necessary to understand the long-term safety, scalability, and specificity of CV-based drug delivery systems. Moreover, the interactions of CVs with diverse cell types within the brain and the potential for customized payloads remain key areas of interest.

Optimism in the Scientific Community

“These findings represent a significant step forward,” says Dr. Antimisiaris, one of the lead authors of the study. “We are not just looking at a new method of drug delivery, but at a new paradigm for therapeutic interventions in brain diseases.”

The Ripple Effect in Medicine

The interdisciplinary nature of this research bridges several fields. The coming together of experts in cell biology, pharmacology, engineering, and clinical medicine indicates a future where therapy development is integrally tied with advanced drug delivery technologies.

Industry Perspectives

Pharmaceutical companies are keenly monitoring advancements in CV technology. Drug delivery systems that could cross the BBB open new markets and possibilities for treatments that were previously deemed too challenging.

References

1. Marazioti, A., et al. (2019). Cellular Vesicles: New Insights in Engineering Methods, Interaction with Cells and Potential for Brain Targeting. The Journal of Pharmacology and Experimental Therapeutics, 370(3), 772-785. [DOI: 10.1124/jpet.119.257097] 2. Anselmo, A. C., & Mitragotri, S. (2016). Nanoparticles in the clinic. Bioengineering & Translational Medicine, 1(1), 10-29. (https://doi.org/10.1002/btm2.10003)
3. Lai, C. P., & Breakefield, X. O. (2012). Role of exosomes/microvesicles in the nervous system and use in emerging therapies. Frontiers in Physiology, 3, 228. (https://doi.org/10.3389/fphys.2012.00228)
4. Saraiva, C., et al. (2016). Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases. Journal of Controlled Release, 235, 34-47.(https://doi.org/10.1016/j.jconrel.2016.05.044)
5. Veiseh, O., et al. (2015). Precision medicine: Targeted nanoparticle systems for therapy and diagnostics. Advanced Healthcare Materials, 5(1), 37-71. (https://doi.org/10.1002/adhm.201500682)

Keywords

1.  Cellular Vesicles Drug Delivery
2. Blood-Brain Barrier Targeting
3. Nanoparticle Therapeutics
4. Brain Disease Treatment
5. Advanced Drug Delivery Systems

About the Journal

The Journal of Pharmacology and Experimental Therapeutics, established in 1909, continues to lead the exploration of the frontiers of pharmacology and the development of new and vital drugs influencing systems biology, molecular pharmacology, and clinical therapeutics.

Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics