User:Audrickya29/Transdermal patch

Micro Needle Patch Size Comparison

A transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream. An advantage of a transdermal drug delivery route over other types of medication delivery such as oral, topical, intravenous, intramuscular, etc. is that the patch provides a controlled release of the medication into the patient, usually through either a porous membrane covering a reservoir of medication or through body heat melting thin layers of medication embedded in the adhesive. The main disadvantage to transdermal delivery systems stems from the fact that the skin is a very effective barrier; as a result, only medications whose molecules are small enough to penetrate the skin can be delivered by this method. The first commercially available prescription patch was approved by the U.S. Food and Drug Administration in December 1979. These patches administered scopolamine for motion sickness. In order to overcome restriction from the skin, researchers have developed microneedle transdermal patch (MNPs). Consisting of an array of micro needles, MNPs allows a more versatile compound or molecule to be passed through the skin without having to micronize the molecule beforehand; While, still holding the advantage of controlled release medication and simple application without medical professional assistance required. With advanced MNPs technology, drug delivery can be specified for local usage, for example skin whitener MNPs that is applied in the face's skin. Furthermore, many types of MNPs are developed to penetrate different tissues other than skin. Such as internal tissue: Mouth, digestive track, etc. This promotes more direct and faster access delivery to reach the targeted area, and also guarantees that the molecule intended will penetrate the tissue without any problem.

Microneedle Patch (MNPs)

MNPs May Puncture Stratum Corneum to Deliver Directly to Dermis Layer.

Microneedle Patch(MNPs) is a type of transdermal patch that holds its advantage, but reduces the disadvantage of basic transdermal patch. Embedding micro needles as many as 102-104 needles per square centimeter of patch, encapsulated or coated with intended drug, MNPs can easily pass skin tissue known as stratum corneum that is roughly 20 μm in thickness, allowing up to the size macromolecule to pass. The development of MNPs is mainly because selective transdermal patch can deliver smaller size or micronized molecules such as nicotine and birth control that easily diffuse and penetrate the skin, but lack in delivering macro or large size molecules. The 100-1000 μm needles spread across the patch, making sure patients will not feel any discomfort from the patch. There are two types of needles used in MNPs, the first one is non-water soluble needles made out of metal, ceramic, or polymer, and the second one is water soluble needles made out of saccharides or soluble polymers.

Other than skin patches, MNPs can also be engineered to deliver molecules in different tissues. Some that are under development include internal surfaces: Mouth, vagina, gastrointestinal tract, and vascular wall; and external surfaces: skin, eye, fingernail, anus, and scalp. Helping to target a more specific area of wanted delivery, without having to solely rely on diffusion on blood flow like a normal transdermal patch.

MNPs Drug Delivery

As mentioned earlier, MNPs deliver more efficient delivery compared to topical or oral intake. In drug delivery study, researchers want to gain faster peak concentration (Cmax) in MNPs compared to other methods. Study shows that MNPs reach peak concentration as fast as 20 minutes (tmax), while oral intake reaches peak concentration in tmax of one hour. Furthermore, the Cmax from MNPs is higher up to six times, compared to oral intake. Making the delivery fast and the body gets the most concentration of intended drugs. This value is only matched with direct injection, but with skin trauma and people with needle phobia, MNPs might be an alternative to reach roughly the same time and concentration.

In order to get more direct local delivery, MNPs can be used in different tissues other than the skin. In Table 1, there are at least five internal surfaces that MNPs have been studied for its delivery and four other external surfaces other than the skin.

Table 1: Tissues Studied for MNPs Delivery

Internal Surface	External Surface
Mouth	Skin
Vagina	Eye
Gastrointestinal Tract	Fingernail
Vascular Wall	Anus
	Scalp

Types of Microneedle

There are many types of microneedle today that are differentiated by the shape and characteristic. The types include: Dissolvable MNPs, solid non-soluble MNPs, and hollow MNPs. Different MNPs may be chosen depending on the situation and the drug properties.

Soluble or Dissolvable MNPs

One of the types of MNPs are water soluble needles made out of soluble polymers or saccharide. However, dissolvable needles cannot efficiently deliver drugs to the dermal layer. Drug maximum concentration cannot be carried out to the skin, as the needles will dissolve beforehand. Luckily, researchers have developed a water insoluble backing layer, making the needle to last longer in the human body environment. This solution enables the drug to deliver efficiently more than 90% from the MNPs in five minutes in the skin.

Non-soluble or Undissolvable MNPs

Other than dissolvable MNPs, needles can also be made out of metal or ceramic that will not dissolve in the body environment. These coated drug needles can deliver consistent concentration of drugs without the needles dissolving in the body. This kind of MNPs has better performance, but compared to the soluble MNPs, metal or ceramic MNPs are the older version of MNPs. Even if the patches are small, the metal or ceramic MNPs may cause several waste issues. Recycling the metal and ceramic are very hard, as the quantity is very small to overcome the cost to recycle. That is why researchers try to develop the dissolvable MNPs with similar characteristic and performance of drug delivery in non-soluble MNPs.

Hollow MNPs

Among all of the MNPs, hollow needles allow a bigger amount of delivery up to 200μL. The mechanism mimics the operation of a hypodermic, but the fabrication is hard and complex. The hollow needles introduce a potential failure if the insertion is improper. That is why, among the others, hollow MNPs is the least popular because of the complex manufacturing and applying proccess.

Advantage

Disposing Needlestick Might Cause Injuries and Transmission of Pathogen.

1. The MNPs may puncture the skin surface, enabling rapid onset of drug bypassing directly into the dermal capillaries.
2. Painfree.
3. Can be localized to provide direct access to the intended tissues.
4. Less dependent on skilled medical workers, as MNPs can be administered safely by the patient itself.
5. Some drugs have poor solubility in water, with MNPs insoluble drugs and compounds can be directly "injected" to the dermal layer. Further enhancing the transdermal delivery of insoluble drugs.
6. Better safety compared to needle and syringe method (needlestick). Less waste, eliminate pathogen transmission, and injuries. At least 300,000 needlestick related injuries occured in the US annually, with disposal contribute to almost half of the injuries.

Application

MNPs as Vaccine Delivery Platform

A Set of Conventional Vaccine Apparatus Needed to be Transported.

MNPs vaccination might be an alternative from direct injection. Able to deliver bigger molecules than transdermal patch, MNPs can also deliver bioactive molecules with different physical sizes. Meaning that inactive virus or pathogen can be introduced in the body without discomfort or skin irritation from conventional injection. Possibly it can also reduce the cost of storage that usually needs to be transported in a particular temperature and condition. Stated in cdc.gov website, Dr.Mark Prausnitz, professor in the Georgia Tech School of Chemical and Biomolecular Engineering and co-developer of microneedle, says "A major advantage of the microneedle patch would be the ease of delivery.". The MNPs are small and thin compared to bottles of vial, making it possible to transport in massive quantities in a single trip. Medical waste such as syringes and dirty needles are also eliminated, reducing the possibility of pathogen transmission of blood-borne disease in rural areas.

In a study, measles coated MNPs might be resistant to higher temperature compared to vial transport. Higher temperature resistance is a safe bet in low income countries, where there is no such luxury for refrigeration. Furthermore, the delivery of the vaccine is controlled by the MNPs. Less requiring highly trained medical workers in developing countries to apply the vaccine. However, the study in MNPs measles vaccine is still under development, but opening possibilities in the future for other types of vaccines.

MNPs to Reduce Obesity

Obesity is one of the most popular topics in developed countries nowadays. Researchers have tried to reduce obesity rate using certain drugs, one in particular known as "browning compound. In order to target a certain group of fat tissue, MNPs is utilized and shows that the patch can deliver browning nano particles to a certain group of fat tissue. By doing so, the drug's side effects can be reduced as MNPs are localized. The result shows that in mice experiments in a four weeks period, the white fat of the mice shrunk. Furthermore, an improved metabolism in the mice also signifies that the experiment to reduce obesity using MNPs might be worth testing in the future. If the research has been proved successful, MNPs treatment might be a great choice, as direct injection obesity drugs need medical professional. While here, MNPs can be done by the patient without special skills.

MNPs for Cosmetic and Skin Care

Skin treatment including face whitening agent and dark eye circles serum can also incorporated in MNPs. Its localized property enhance skin whitening delivery to the face area. Even a very specific spot like dark eye circles. By measuring the melanin (dark or black pigment found on the skin) index, subjects that are treated with whitening agents coated in MNPs show lower melanin index, compared to the whitening essence (topical) group. The treatment lasts for eight weeks, and the result shows MNPs might be a promising cosmetic vector because MNPs does not introduce skin irritation and can be engineered to localize or specific parts of the body.

Safety

Micro Needle Patch (MNPs) might be another choice of safety compared to direct injection using candlestick. Not only safety in handling, MNPs also promote better disposal and prevent pathogen transmission. Under extraordinary circumstances, MNPs may cause complication mentioned below.

Skin Irritation

Under a rare circumstances, MNPs may cause skin irritation on people with sensitive skin. Majority of studies show that MNPs do not irritate the skin, but does not close the possibility for sensitive skin group of people.

Improper Application

Especially for hollow MNPs, the not so stiff needles may cause unnecessary puncture to the skin outer layer. Thus may cause trauma to the skin and restricting the performance and flow of the drugs to the body.

Future Development

Because most of MNPs applications are still under development, it is important to note the long effect of the efficiency of the drug deliveries. Furthermore, more research is needed to get information of what molecule can be delivered using MNPs. Disposal is also an important topic, as the small plastic backing may contribute to water pollution remembering the compact size can be easily carried away by wind and water without proper disposal.