Mcroneedles (MN) is a new type of physical permeability-enhancing technology. It consists of multiple micron-scale fine needle tips connected to the base in an array. The needle body is generally 10-2000 microns high and 10-50 microns wide. The length, size and shape of the microneedles can be individually designed according to the needs of the application.
When the microneedle delivers the drug, the active ingredient is loaded into the microneedle array, and the concentration gradient between the drug and the subcutaneous tissue fluid forms a driving force, causing the drug to be slowly released into the body. In addition to the advantages of a transdermal delivery system, it also has the following advantages:
- The transdermal absorption rate is stable.
- Controlling the length of microneedles can avoid touching capillaries and nerve endings, reducing or eliminating pain.
- The method of administration is convenient and can be used by oneself.
The History of Microneedles
In 1958, Alan Richard Wagner proposed the concept of microneedle intradermal injection and applied for a patent, but limited by the preparation technology at that time, microneedles could not be prepared for practical research. Until the patent expired in 1979, there was no breakthrough.
In 1976, based on microneedle intradermal injection, Gerstel and Place first proposed the concept of microneedle transdermal drug delivery, but in the following two decades, no real microneedles were available for experiments.
In 1995, with the development of micro-electro-mechanical system (MEMS) processing technology and the emergence of high-precision semiconductors and microelectronic devices, Hasmhi et al. used etching technology to prepare microneedle arrays on silicon wafers for the first time.
In 1998, Henry et al. of Georgia Institute of Technology in the United States applied microneedles to transdermal drug delivery research for the first time, making microneedle technology enter the formal drug delivery field and triggering an upsurge in the development of microneedle materials until finally realizing industrialization.
Classification of Microneedles
According to the characteristics of microneedles, microneedles can be divided into solid microneedles, hollow microneedles, coated microneedles, dissolving microneedles, and hydrogel-forming microneedles.
Solid microneedles are usually made of metal materials and non-degradable polymers, such as silicon and titanium dioxide, which do not carry drugs themselves. Their function is to puncture the epidermis and form the microchannels required for drug penetration. Therefore, solid microneedles can be used to deliver drugs in two steps: the first step is to make the microneedles puncture the skin surface to form micropores; the second step is to remove the solid microneedles and apply the drug on the microneedle puncture site.
As the earliest developed microneedles, the disadvantages are more obvious. The biggest problem is that the microchannels formed by the pretreatment of solid microneedles will shorten the drug action time due to skin healing within 24 hours. In addition, solid microneedles are prone to breakage due to their high mechanical strength, and the arrays trapped in the body bring safety hazards to patients. At the same time, microchannels are in different dynamic recovery states due to individual differences, resulting in the inability to accurately control the dosage, and there will be errors in the evaluation of pharmacodynamics and pharmacokinetics.
Hollow microneedles are essentially micron-scale micro-syringes. Drugs are preloaded in the hollow structure of the needle body or in the needle cavity. After the hollow needle tip penetrates the skin, the drug enters the body under the pressure of the interstitial fluid concentration gradient to achieve drug delivery.
According to the materials selected for preparation, the hollow microneedles can be divided into silicon hollow microneedles, metal hollow microneedles, and polymer hollow microneedles. Due to their good biocompatibility and flexibility, polymers are the development direction for the preparation of new microneedles.
Among all types of microneedles, hollow microneedles have the largest drug-loading capacity due to their hollow structure and can adjust the release rate to achieve precise drug delivery, but they also have some disadvantages.
Coated microneedles are also known as surface drug-loaded microneedles. The drug is attached to the surface of the microneedle by infiltration, coating or drug loading outside the needle. After the microneedle penetrates the skin, the drug dissolves in the skin and enters the intercellular fluid and is delivered into the human body. Coated microneedles are mainly used to deliver water-soluble drugs. The release rate of drugs in the skin is fast, the bioavailability is high, and the dosage is easy to control. It is also suitable for small molecule and macromolecular drugs. Moreover, the coated microneedles can be reused.
However, the disadvantages of coated microneedles are also obvious. For instance, the drug loading capacity is not high, and it is only suitable for treatment that require a small amount of drug.
Dissolving microneedles are biodegradable polymer materials and drugs prepared into microneedles. After piercing the skin, the needles made of degradable materials will gradually degrade in the microenvironment, and the drugs will be released synchronously. Molecules pass through the stratum corneum barrier and are absorbed into the body through the subcutaneous tissue. Dissolving microneedle drug delivery does not need to remove the needle body after forming micropores to deliver the drug like other microneedles, which greatly improves patient compliance. At the same time, the non-reuse of microneedles also reduces the risk of cross-infection.
At present, dissolving microneedles are the mainstream of the entire microneedle industry, and their main advantages are high-efficiency drug delivery, precise control of drug loading and more.
Hydrogel-forming microneedles are prepared from a hydrogel polymer matrix. The preparation method is similar to that of dissolving microneedles. It is considered to be a subtype of dissolving microneedles. It is usually prepared by cross-linked hydrogel or super-swellable polymer. When the hydrogel-forming microneedle is administered, the microneedle array quickly absorbs the interstitial fluid into its grid after piercing the skin. At this time, micropores that can deliver drugs are generated in the gel, and the drugs are delivered into the human body through the micropores of the hydrogel under the action of penetration and diffusion of interstitial fluid.
Cryomicroneedles are a new type of microneedle technology recently developed by scientists at the City University of Hong Kong. This refers to a cryomicroneedle shorter than 1 mm, which is loaded and stored with living mammalian cells in vivo and delivers therapeutic cells into the skin layer. When administering the drug, the patch-shaped device loaded with cryomicroneedle arrays is placed on the skin, and the cryomicroneedles penetrate into the skin, detach from the base of the device and melt, releasing the cells in the needle body, which then migrate and proliferate in the skin. This innovative microneedle can be stored for several months under normal storage conditions and is easy to transport and use.
Overall, cryomicroneedles have opened up a new era of microneedle application in the field of cell therapy, providing another simple, safe, efficient, and minimally invasive development strategy for cell therapy.