Skin – the chasm that drugs can hardly cross In the past, human beings usually took two methods to cure diseases, taking medicine or injections. But medicine has the problem of low utilization of drugs and slow treatment, while injections not only produce pain and harm the body’s normal tissues, but also have the problem of possible cross-infection and environmental pollution of injection tools. Of course, sometimes it is the practical nurse who may be the lingering nightmare in your readers’ minds. In order to improve this situation, transdermal drug delivery systems with patches as the main therapeutic means have received attention as a new direction of research since the 1970s. This method of drug delivery facilitates long-term drug administration and greatly reduces the fear of drugs in patients. However, due to the existence of skin stratum corneum, the permeability of the skin is poor. In the natural state, only drugs with relative molecular mass less than 500 and good lipid solubility can penetrate into the dermis and enter the body circulation via capillaries. The water-soluble drugs, which dominate in clinical applications, and the biomolecules that have emerged in recent years, are extremely difficult to be absorbed percutaneously. Although physiologically, the skin is a barrier to prevent excessive water loss and the invasion of external pathogens and toxins. However, in the case of dermal drug delivery, this barrier constitutes a major obstacle to the transdermal delivery of drugs to the dermis. The origin of microneedling: taking medicine is slow, injections are painful, and creams are unable to reach the deeper layers of the skin, so is there a method that is as effective as injections but as painless as creams? This question is also difficult for many scientists. One day in the hospital, scientists saw a child was crying loudly: “You lied to me! You said the injection is as painless as a mosquito bite.” This question woke up the dreamer, the same is broken skin injection, why the injection so painful, mosquito bites but no feeling? Scientists through the analysis of existing experience and literature research, clear the mosquitoes in the blood to avoid causing pain in three ways: 1, numbness. They secrete saliva, which contains proteins that cause numbness. 2, bundles of serrated design of the mouthparts. 3.Vibration drive. Piercing the skin, the secretion or draw blood part will vibrate, thus reducing the force required. Inspired by the mosquito’s “painless blood sucking” function, scientists have developed a micro-nanometer syringe needle, or microneedle, modeled after the structure of the mosquito’s mouth needle; the mosquito’s mouth needle has provided important inspiration for the structural design and application of artificial microneedles in terms of piercing method, needle body shape and needle tip structure. What is a microneedle? Microneedle body is a micron-level structure, it is hollow or solid structure, similar to our commonly used medical injection needle, can be administered mainly in a substrate array of microneedles, that is, in accordance with a certain array arrangement distributed on the substrate. The length of the microneedles varies, mainly because the thickness of the epidermis and dermis varies between the human body, and different parts of the body require different lengths of microneedle arrays. Microneedles can penetrate the stratum corneum of the skin and reach the epidermis of the body, but at the same time they do not touch the dermis where the painful nerves are distributed, so that the drug penetration can be promoted without causing pain or skin damage. The structure of microneedles is so small that the epidermis and dermis of the skin can be understood that the damage caused by microneedles to the skin is not greater than that caused by people’s daily skin damage. Microneedles were first used in the field of transdermal drug delivery in 1998, which attracted the attention of many researchers in the field of transdermal drug delivery, and since then many different types of microneedles have been developed by researchers. Tip: Why is microneedling painless? The reason why microneedling is painless is due to the structure of the human skin and the structure of the microneedle. Human skin can be divided into three layers from the surface to the inside: the stratum corneum, the active epidermis and the dermis. Studies have shown that the stratum corneum, formed by the accumulation of dead keratinocytes, has a solid texture and forms a natural barrier for drug delivery; the epidermis contains no blood vessels and has active cells and a small amount of nerve tissue; the dermis, located in the innermost layer, is the main structure of human skin, and the state of the skin in this layer determines the overall condition of human skin; it contains a large amount of nerve tissue, which senses external stimuli, and also contains many active cells and vascular tissue. In order to ensure high drug penetration without significant pain when the microneedle is inserted into the skin, the microneedle should penetrate the stratum corneum and epidermis without entering the dermis, which is rich in nerves. Therefore, during the design of microneedles, the overall structure of the skin is taken into account to ensure that the height of the microneedle is greater than the thickness of the stratum corneum, so that the microneedle can break through the barrier of the stratum corneum to the delivery of drug active ingredients to reach the deeper layers of the skin, and at the same time, in order to achieve painless microneedling, its height should not exceed the sum of the thickness of the stratum corneum and the epidermis. However, in the actual application of microneedles, the design height of microneedles is often greater than the sum of the thickness of the stratum corneum and the epidermis, which is due to the elasticity of the skin, the unevenness of the surface, and the joint influence of many factors such as the piercing method and the structure of the needle body, etc. When microneedles are pierced into the skin, the needle body does not penetrate all the way into the skin; in addition, because microneedles belong to the micro and nano structure, even if the tip of the microneedle pierces into the dermis, it does not necessarily In addition, because microneedles are micro and nano structures, even if the tip of the microneedle pierces the dermis, it does not necessarily touch the nerve cells and blood vessels; therefore, in practice, the height of the microneedle is high in order to ensure the effectiveness of the use of microneedles.