BLOG: Molecules for drug delivery

Technological advances in the world of medicine are steering engineering research towards ways of delivering drugs to our body through products that are far more complex than a pill or a syrup. The idea of using small molecules that can travel through our body carrying medicine is gaining popularity and beginning to show groundbreaking results.

A fascinating, yet challenging, goal for today’s scientists is to engineer small molecular spheres — called drug carriers — that can effectively deliver anticancer agents to our brain. More specifically, the vision is to ensure that these molecules are biodegradable so they can be easily expelled from the body after treatment, that they successfully target and efficiently penetrate dense tumor tissues, and that they do so stealthily to prevent attacks or barriers from our immune system.[1] Molecules with such distinct characteristics could enhance drug efficacy, thus increasing cancer survival rates.

Besides surgery, which is the most common tumor removal procedure, there exist other treatments that involve the delivery of anticancer agents to the brain. As of today, the most common delivery procedures include direct exposure to radiation to eliminate cancerous tissue[2] and other invasive delivery methods,[3] including the injection of fluids directly to a tumor or the nervous system. These approaches are undesirable because they can have toxic consequences on the patient’s neural system and overall health.[3]

To ensure that anti-cancer drugs and therapies result in as little harm as possible, engineers have researched molecules that can travel throughout our body without being as damaging to the patient as conventional methods. However, finding suitable carriers to bypass our body’s defense systems — more specifically, the ones in our brain — has been particularly challenging due to an obstacle in our central nervous system that impedes the transportation of drugs from the bloodstream to the brain tumor site.[3] This obstacle is called the blood-brain barrier (BBB), a highly selective barrier that impedes entry of most blood-borne substances[4] and, if bypassed, allows molecules to circulate through the nervous system and subsequently target the cancerous tissue. The precision of the targeting is also a significant problem that has to be tackled by engineers.[1][5]

According to an article titled Advances in targeted drug delivery,[3] there are numerous carriers available today that have the distinct ability of either encapsulating an anticancer agent inside a storage unit or containing such an agent in a way that it is dispersed throughout[3] the molecule. These carriers are usually made up of minuscule polymers and have different characteristics that make them competing solutions for targeted drug delivery.[6] For example, engineers have developed a suspension of small particles in water that is able to bypass the BBB by diffusing down a concentration gradient “from an area of high concentration to an area of low concentration”.[7][8] Some advantages of these particles are that they can be administered in many ways (e.g., orally, nasally, injected), that they can be modified so that they target different areas of the brain, and that they are able to retain several drugs.[3][6] Nonetheless, in high concentrations the efficiency of such particles is diminished, which means that the BBB will not allow them to trespass to reach the tumor.[6] Other issues include their potential drug toxicity,[3] from leakages of the anti-cancer agents, and also their large surface area, which can lead to the particles joining together and possibly becoming a gel.

Consequently, a group of researchers from UCL have recently developed a new solution which involves molecules that can be modified to be less toxic and that have less probability of leaking the anti-cancer agent.[3][9] These molecules can encapsulate the drugs because they have two sides: one that repels water; and one that is attracted to it. When in water, these properties “cause them [the carriers] to self-assemble into spherical structures”[5] that are able to penetrate the BBB and navigate autonomously through our nervous system to target the tumor.[9] One of the captivating properties of these carriers is that their physical properties can be modified. For example, the carrier created by UCL researchers is able to propel itself through our nervous system by breaking down glucose and releasing the byproducts on only one side of the molecule, thus “pushing the molecule forward”.[5][9] This increases targeting efficiency of the carrier, because areas around brain tumors have higher glucose concentrations, causing the carrier to propel itself towards the cancerous tissue.[5]

These molecules therefore pose great advances for targeted drug delivery for cancer. The impact of this solution on the future of drug delivery relies on the molecule’s increased efficiency, the mechanism it uses to target tumors, its biodegradability and its ability to carry large doses of an anti-cancer agent.[9] Nevertheless, producing the molecules in large quantities is one of the biggest issues of today, as building them is extremely complex and costly.[6][10] Hence, finding alternate production methods that could reduce these costs and complications could take us even closer to realizing the vision.

In conclusion, drug carriers engineered through nanotechnology are on the brink of excellence; their moldable properties and stealth are characteristics that are sought after for drug delivery in the brain, and subsequent research must look at scaling up production to optimize efficiency and reduce the difficulties of production to meet the large demand for anti-cancer drugs.

This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

References

  1. Guan, L., Rizzello, L. and Battaglia, G, Polymersomes and their applications in cancer delivery and therapy, Nanomedicine. 10, pp. 2757–2780, 2015.
  2. Malignant brain tumour (cancerous): Treatment, National Health Service UK. Accessed 28 November 2017.
  3. Meng, J., Agrahari, V. and Youm, I., Advances in Targeted Drug Delivery Approaches for the Central Nervous System Tumors: The Inspiration of Nanobiotechnology, Journal of Neuroimmune Pharmacology. 12, pp. 84–98, 2016.
  4. Ballabh, P., Braun, A. and Nedergaard, M., The blood–brain barrier: an overview, Neurobiology of Disease 16, pp. 1–13, 2004.
  5. Mo, C., Drug-Carrying “Nanoswimmers” Could Slither Past the Brain’s Cellular Defenses, Scientific American, 7 August 2017.
  6. Fonseca-Santos, B., Chorilli, M. and Palmira Daflon Gremião, M., Nanotechnology-based drug delivery systems for the treatment of Alzheimers disease, International Journal of Nanomedicine 1, pp. 4983–5003, 2015.
  7. GCSE Biology - Movement across cell membranes - Revision 2, BBC Bitesize, 2017.
  8. Particulate Dispersion, Radical Polymers, 2017.
  9. Joseph, A., Contini, C., Cecchin, D., Nyberg, S., Ruiz-Perez, L., Gaitzsch, J., Fullstone, G., Tian, X., Azizi, J., Preston, J., Volpe, G. and Battaglia, G., Chemotactic synthetic vesicles: Design and applications in blood-brain barrier crossing, Science Advances 3, pp. 1–12, 2017.
  10. Zhu, X., Anquillare, E., Farokhzad, O. and Shi, J., Polymer- and Protein-Based Nanotechnologies for Cancer Theranostics, Cancer Theranostics 16, pp. 419–436, 2014.

About the Author

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