There are biological barriers that protect the human body from various kinds of detrimental and foreign substances. Although these barriers defend our body, sometimes we need medicine to help us heal faster or to prevent serious diseases. The pharmaceutical industry is one of the biggest in the world. A significant amount of resources is devoted to finding easier, cheaper, and more effective cures for many illnesses.
The drug molecules that are supposed to be curing us also need to overcome our body’s defense mechanisms. Let’s look at some of the body’s defenses and the way drugs overcome them, before we examine an unexpected inspiration for a new method of delivering drugs.
Our skin is the largest barrier preventing toxic substances from getting inside our bodies. The intestinal mucosa or the blood-brain barrier is a physiological defense barrier. If a drug molecule can pass through these barriers, the next step to be overcome is the biochemical barrier, where myriad enzymes play a role. Therefore, drug molecules have to be designed with optimal physicochemical properties. These include the proper size, charge, and hydrophilicity (water solubility) to ensure their permeation across our bodies’ biological barriers.
There are a few types of drug delivery systems. They are oral, pulmonary (via inhalation), intravenous (via injection), and transdermal. All of them have their own advantages and limitations.
For oral applications, a drug molecule needs to traverse the epithelial layer of the gastrointestinal tract. Thus, there are many factors which have to be taken into consideration for enhancing the delivery of molecules through the intestinal mucosal barrier. Many of the newer drugs on the market are composed of peptides and proteins, and they cannot be administered orally due to their relatively larger size compared to smaller drug molecules.
The delivery of drugs via traditional injection provides better bioavailability; however, this route has low patient compliance due to injections being painful and accidental needle-sticks. Hypodermic injections also generate dangerous medical waste and pose the risk of disease transmission by needle re-use, especially in developing countries.
Transdermal drugs have become an important form of medication in recent years, as they are non-invasive or minimally invasive. Transdermal drugs have many advantages over other drugs, such as high patient compliance due to the easy accessibility of skin, the avoidance of the gastrointestinal tract, and that they can be self-administered.
The main problem with transdermal drugs is that the skin is a highly effective barrier. The outermost layer of skin, the stratum corneum, is mainly composed of dead carneocytes embedded in lipid layers, and has a thickness of 10-15 μm. This packed structure offers a substantial barrier to the delivery of both small hydrophilic (water soluble) and high molecular weight drugs. Only small lipophilic molecules, which can dissolve in lipids, can pass through the skin. Therefore, alternative methods and devices are needed to deliver hydrophilic and macromolecular (larger) drugs through the skin in a controlled manner.
Numerous chemical and physical methods have been attempted with the purpose of increasing skin permeability for easier drug delivery. As the name suggests, micro-needles are micron-size needles that are applied for transdermal vaccinations, as well as drug and gene delivery. Researchers hope they will increase skin permeability via forming micron-sized channels in the skin, thereby allowing the delivery of therapeutics across the skin barrier. In addition, by careful control of the micro-needles’ mechanical strength and length, it is possible to deliver drugs across the dermal barrier while evading the nerves, thus resulting in a painless administration.
Micro-needles must have a high degree of stiffness (resistance to bending) and enough strength for a successful insertion into the skin. If they’re too flexible, they won’t insert; if they’re not strong enough, they’re fracture. A variety of materials are used to manufacture micro-needles, and they include silicon, glass, metals (e.g. stainless steel, titanium, and nickel-iron), and polymers. Current micro-needle technology is based on imitating the present hypodermic needle geometry and miniaturizing it utilizing a silicon micro-machine process. The designs are fabricated onto a substrate where hundreds of micron-sized needles are formed, and then these micro-needles can be either pressed or scraped on the skin, forming microscopic holes. As a result, skin permeability increases by approximately four degrees of magnitude, allowing the easier delivery of medicine.
The ideal micro-needle needs to be extremely small, with an inner diameter of 10-20 μm. It is very challenging to prepare such small needles, ones that are also strong and flexible. Fortunately, we have a living example to guide our designs: female mosquitos.
The world’s most advanced micro-needles are found in mosquitos. Thus, scientists and engineers have begun trying to mimic a female mosquito’s bite – that is, the way they suck blood from our bodies while also leaving behind their itch-causing enzymes. If such a breakthrough can be achieved, blood drawing or drug injection may be performed painlessly. Researchers from North Carolina State University indicate that if a “synthetic mosquito” capable of drawing blood painlessly can be developed, millions of diabetics worldwide who must draw blood several times a day for glucose monitoring will be able check their glucose numbers without pain.
Mosquito needles are made of two main parts: the fascicle and proboscis. The general shape of a female mosquito needle is a core-sheath structure where the fascicle is the main needle puncturing the skin and drawing blood and the proboscis acts as a surrounding and protective layer for the inner needle. Interestingly, only female mosquitos bite, since their need for human blood is only for the purpose of developing their eggs, not for their nutrition.
Ideally, a micro-needle would mimic the structures of a mosquito’s needle, including the mechanism by which the mosquito penetrates the skin and draws blood. This would make for the painless treatment of many diseases.
To prepare a micro-needle based on a mosquito needle would require extensive knowledge of chemistry, material science, mechanical and structural engineering, and fluid dynamics. After resolving any scientific challenges, these needles would need to be manufactured in high quantities to reach the many people in need. This would require scaling up the fabrication methods in a safe and compliant facility. For such widespread production to happen, the process would have to be widely adopted by patients.
In summary, if researchers can mechanically mimic a mosquito needle, it would be a great achievement in the development of advanced micro-needle technology. It’s incredible that the solution to a major medical problem – the efficient delivery of drugs and vaccines – is already present in nature, at our disposal.
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