Brain Diseases’ Worst Enemy: Nanoparticles

Understanding Nanotechnology through Targeted Drug Delivery to the Brain

Aahaan Maini
10 min readNov 23, 2020

This article gets pretty scientific in some parts, consider bookmarking it, brushing up your knowledge on targeted drug delivery and then returning to get maximum value.

Nanotechnology has been viewed as one of the most innovative technologies of our generation, with the potential to revolutionize our future.

However, very few people understand what Nanotechnology truly is. Let’s start off by breaking it down into nano and technology. The word technology isn’t just iPhones or Cloud Computing, but rather it is the branch of knowledge that deals with applied sciences.

The nano in nanotechnology gets a little more complicated. Everything to do with nanotechnology is referred to at the nanoscale, which is between 1 and 100 nanometers. In short, 1 nanometer is one-billionth of a meter.

Therefore, by definition, Nanotechnology is the control and fabrication of matter at the nanoscale.

To put things in perspective, consider one of the smallest things we can see with the naked eye: a single human hair. Now here is where it gets really crazy. A single human hair is around 90,000 nanometers wide.

A Nanowire (highlighted in red) curled in a loop on a single human hair. Source

Nanotechnology is so revolutionary because the physical and chemical properties of materials change at the nanoscale and can be manipulated. Boiling and melting points, colour, fluorescence, conductivity, magnetic permeability, and reactivity are examples of these properties.


Nanoparticles are one of the main aspects of nanotechnology. They are particles of matter with at least one dimension in the nanoscale.

There are over a dozen types of nanoparticles (see below), each with its own structure and its own purpose.


In this article, I’ll be focusing on only the nanoparticles that are used for targeted drug delivery to the brain.

The Magic School Bus in Real Life

Remember the classic TV show The Magic School Bus, where the teacher and her class would go on the school bus, it would shrink down and then travel throughout the body? Targeted drug delivery is essentially that, except instead of students, there are drugs or medication

Targeted Drug Delivery is a group of technologies that deliver and control the release of drugs to very specific parts of the body.

The way they work is by using nanoparticles, or other materials at the nanoscale, to bind to certain target receptors found in the specific cells.

For example, the most commonly used case of targeted drug delivery is in cancer treatment. In brain cancer specifically, nanoparticles can use their surface receptors to bind to tumour cells and increase the accuracy and specificity of tumour detection.

Why Nanotechnology?

The blood-brain barrier (BBB) is a highly selective semipermeable membrane whose job is to stop substances in the blood from entering the central nervous system and coming into contact with neurons.

A highly selective semipermeable membrane is a barrier found in our bodies, that only allows very few molecules and particles to pass through. It is made out of various lipids, proteins and carbohydrates.

A simplified makeup of the blood-brain barrier. Source

The blood-brain barrier permits essential nutrients and gases from the bloodstream while blocking larger entities such as microbes, immune cells and most drugs from entering. Therefore, arguably the hardest challenge with delivering targeted medicine treatments to the brain has been crossing the BBB.

The BBB is the strictest barrier in our bodies, restricting 95% of substances. It is located at the brain capillaries and made up of endothelial cells, pericytes, astrocytes and microglia, which are all different types of cells.

There are 3 main ways that particles can be crossed over the BBB:

  1. Passive Delivery
  2. Temporary Disruption of the BBB
  3. Active Delivery

Passive movement is the natural diffusion of particles and molecules through the BBB. There are several factors apart from the size of the particles, that considered before they are allowed to pass through the BBB. It is the ionization of the drug, its molecular weight, its protein binding ability and finally its lipophilicity (its ability to resolve in a solvent).

Temporary disruption of the blood-brain barrier involves using a variety of chemicals to permeabilize (allow a lot more particles to pass through) the BBB. This method isn’t widely used because the barrier plays a vital role in the safety and health of the brain and central nervous system, and when disrupted, it can cause major damages to the brain.

Active delivery is where the pot of gold lies. Active delivery uses nanotechnology-based drug delivery systems to overcome the challenges and create innovative ways to deliver the drugs, all while maximizing benefits and minimizing drawbacks.

Nanotechnology plays the biggest role in active delivery, which is what I am going to be focusing on, for this article. The other major challenge with traditional targeted drug delivery is being detected by the Reticuloendothelial system.

The Reticuloendothelial system (RES) is a system in the body whose job is to remove dead or abnormal cells and tissues and remove any foreign substances. This is once again another major challenge for targeted drug delivery in the entire body, not just the brain.

Nanotechnology can also solve this problem as nanoparticles can transform themselves to prevent getting recognized by the RES and flushed out of the body.

Blowing Chemotherapy Out of the Water

Through the introduction of multifunctional nanoparticles into targeted drug delivery, it has been able to overcome one of the biggest challenges with chemotherapy: systemic toxicity.

An example of a multifunctional nanoparticle. Source

Multifunctional nanoparticles are nanoparticles that can deliver up to several different types of drugs.

Systemic toxicity is a possible result and side effect of chemotherapy, in which it can severely/permanently damage surrounding tissues or even become life-threatening. With nanotechnology, you don’t have to worry about any of that.

The majority of the content for the rest of the article is based on the research from Modi et al., 2010, Kumar et al., 2017 and Karanth et al., 2018.

Polymeric Nanospheres and Nanocapsules:

Nanospheres and nanocapsules are two similar types of nanoparticles.

Nanocapsules have a cavity where the drugs are placed which surrounded by a polymer membrane and then protected by a thin shell. Nanospheres have a very dense polymer matrix, which the drugs are then woven into and surrounded by a similar thin shell.


In order to cross the BBB and avoid RES recognition, both the nanospheres and nanoparticles manipulate their surface properties. In simpler terms, what this means is that it changes the way it looks, feels and acts on the outside.

The advantage of using these nanoparticles is that scientists can load large amounts of the desired drug and due to the secure containment, they prevent degradation of the drug as it travels through the body.

Kreuter et al., 2003 and Steiniger et al., 2004 were able to successfully use nanospheres and nanocapsules to deliver the drugs Doxorubicin and Dalargin into the brain and central nervous system of mice and rats.

Polymeric Nanogels and Nanosuspensions:

Nanogels are a network of physically or chemically linked polymers. Nanosuspensions is the process in which the drugs are colloidally (evenly) in the nanogel.


Nanogels and nanosuspensions are created in tandem by a process called Emulsification Solvent Evaporation, in which they can incorporate RNA, DNA, proteins, and drugs with a low molecular mass, into the nanogel.

In short, Emulsification Solvent Evaporation occurs when the drugs are broken down into sub-nanoscale sizes and dispersed into a liquid form of the polymer. The solvent in which this all takes place then evaporates, resulting in a Nanogel with Nanosuspension of the drug.

The advantages of using nanogels are its drug loading capacity of 40–60%, the fact that it can deliver non-liquid soluble drugs through nanosuspension and its rate of release. Nanogels are able to enable a slow, controlled release of the drugs.

Vinogradov et al., 2004 have been able to incorporate oligonucleotides, a type of DNA or RNA molecule, and have been able to successfully deliver them to the Brain.

Polymeric Nanomicelles:

Nanomicelles are, by far, the most unique nanoparticles out there, due to their structure. Polymeric Nanomicells are types of nanoparticles in which all of their benefits lie in said structure.

Polymeric Nanomicelles have a core-shell structure, with a hydrophobic core and a hydrophilic corona (shell). The core repels water (hydrophobic) and the corona, attracts water molecules (hydrophilic). The core holds hydrophobic drugs and all other hydrophilic materials like DNA are held on the corona.


The hydrophilic corona masks the drugs and prevents the RES from capturing it. Once it reaches its destination, the drugs are released through diffusion.

In the delivery process, peptides are used for targeting and binding to the receptors in the desired cells.

Nanomicelles offer several advantages, including one of the most efficient pharmacokinetics, which is the journey the drug takes through the body before reaching its destination. It is able to penetrate tissues extremely well and achieve a very high control when releasing the drugs.

Nanomicelles have been successfully used by Miura et al., 2016 in the exact scenario we are discussing: for delivering a chemotherapy drug over the BBB and to the desired location in the brain.

Polymeric Nanoliposomes:

Nanoliposomes are the fan-favourite nanoparticles for targeted drug delivery. They are vesicles that are made of singular (or occasionally multiple) lipid bilayers, surrounding an aqueous core. A lipid bilayer is a membrane of 2 lipid molecules, surrounding a watery core. The drugs are added to the core.


The surface of nanoliposomes reduces opsonization, which is the flagging of foreign particles, and therefore reduces recognition by the RES and BBB. Specifically, it uses Polyethylene Glycol, a compound often used in the health industry, to change the surface and avoid detection.

These liposomes use monoclonal antibodies to identify exactly where to go to deliver the drugs. Monoclonal antibodies are artificially created proteins, that mimic the antibodies in our bloodstream created by white blood cells.

These antibodies function as ligands, which are molecules that bind to specific elements or compounds, in order to bind to certain receptors found on the cells of the desired location.

In much simpler terms, this means that they function the same way antibodies in our bodies do when they identify and pinpoint harmful cells that have been in our bloodstream before.

Like I mentioned before, there is a reason nanoliposomes are the fan-favourite! They can achieve extended circulation times by decreasing the size of the nanoparticle, they are able to transport large quantities of the most drugs out of any other nanotechnology system.

In this case, the successful experiment was conducted by Shi et al., 2001 where they used nanoliposomes to deliver Doxorubicin to the cells of a central nervous system and brain tumour.


Dendrimers are spherical nanoparticles that are made up of repetitive tree-like structures, that stem from a singular core or multiple cores. The core is the central part to which all the primary levels of branches are connected to. The primary branches then split in the shell, then the split branches split again, and so on. The final layer consists of the terminal branches. The unique branching structure allows for the encapsulation of drugs.


The advantages of using dendrimers are its high loading capacity of drugs due to the countless small cavities, its ease when penetrating barriers and tissues and extremely high bioavailability of the drug. Bioavailability is the amount of the drug that actually reaches its destination in the body.

Srinageshewar et al., 2017 have successfully used dendrimers to cross the BBB in mice.

Iron Oxide Nanoparticles:

Targeted Drug Delivery in the brain has also been accomplished using magnetic nanoparticles, made out of iron oxide.

An external magnetic field is used to navigate and steer the nanoparticles to the desired location.


This experiment conducted by Do et al., 2015 used Iron Oxide nanoparticles to deliver brain-derived neurotrophic factors (a protein) across the BBB.


To summarize, various types of nanoparticles can be and are being used to find more efficient methods to work around the challenges and deliver drugs into one of the most difficult places in our body, the brain.

Specifically, the types of nanoparticles discussed today were Nanospheres, Nanocapsules, Nanogels with Nanosuspension, Nanomicelles, Nanoliposomes, Dendrimers and Iron Oxide Nanoparticles briefly.

Each of these has its own advantages, disadvantages and applications for delivering the drugs to the desired location.

Targeted Drug Delivery with nanotechnology in the Brain can be used to revolutionize the treatments of diseases in the Brain and Central Nervous System, but it doesn’t stop there, nanotechnology can be used to revolutionize targeted drug delivery in the entire body. It doesn’t stop there either, it can be used to revolutionize all healthcare. But no, ok, ok, I’ll stop there, but the point is that nanotechnology does have the potential to change the world.

Now we know that the people in the introduction who viewed nanotechnology to what they thought was its full potential, was only the tip of the iceberg.

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Aahaan Maini

16-year-old ML dev currently building Circulate to tackle the blood shortage in India