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Transdermal patch
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== Microneedle patch == {{Further|Microneedle drug delivery}} The microneedle patch (MNPs) is a type of transdermal patch which retains the advantages, but reduces the disadvantages of basic transdermal patches. Embedding as many as 102-104 needles per square centimetre of patch, encapsulated or coated with intended drug, MNPs can easily pass skin tissue known as the [[stratum corneum]] which is roughly 20 μm in thickness, allowing up to the size of [[macromolecule]] to pass.<ref name=":2"/> MNPs were developed mainly because transdermal patch can deliver smaller size or [[micronize]]d molecules such as [[nicotine]] and [[birth control]] which 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 people 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 [[saccharide]]s or soluble polymers.<ref name=":2"/> MNPs can also be engineered to deliver molecules into other tissues. Some that as of 2018 have been under development include internal surfaces such as the mouth, vagina, gastrointestinal tract, and vascular wall; and external surfaces such as the skin, eyes, fingernails, anus, and scalp.<ref name=":2"/> === 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 concentrations]] (C<sub>max</sub>) in MNPs compared to other methods. Study shows that MNPs reach peak concentration as fast as 20 minutes (t<sub>max</sub>), while oral intake reaches peak concentration in one hour. Furthermore, the C<sub>max</sub> from MNPs is higher up to six times, compared to oral intake.<ref name=":2"/> 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.<ref>{{Cite journal|last1=Ma|first1=Yunzhe|last2=Tao|first2=Wenqian|last3=Krebs|first3=Shelly J.|last4=Sutton|first4=William F.|last5=Haigwood|first5=Nancy L.|last6=Gill|first6=Harvinder S.|date=2014-03-13|title=Vaccine Delivery to the Oral Cavity Using Coated Microneedles Induces Systemic and Mucosal Immunity|journal=Pharmaceutical Research|volume=31|issue=9|pages=2393–2403|doi=10.1007/s11095-014-1335-1 |pmid=24623480 |pmc=4163144 |issn=0724-8741}}</ref> 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. [[File:Схематичное изображение глубины введения активной субстанции.png|thumb|270x270px|MNPs may puncture stratum corneum to deliver directly to the dermis layer.<ref>{{Cite journal|last1=Jamaledin|first1=Rezvan|last2=Di Natale|first2=Concetta|last3=Onesto|first3=Valentina|last4=Taraghdari|first4=Zahra|last5=Zare|first5=Ehsan|last6=Makvandi|first6=Pooyan|last7=Vecchione|first7=Raffaele|last8=Netti|first8=Paolo|date=2020-02-17|title=Progress in Microneedle-Mediated Protein Delivery|journal=Journal of Clinical Medicine|volume=9|issue=2|page=542|doi=10.3390/jcm9020542|pmid=32079212 |pmc=7073601|issn=2077-0383|doi-access=free }}</ref>]] {| class="wikitable" |+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 that are distinguished by the shape and other characteristics. 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. Fortunately, researchers have developed a water-insoluble backing layer, making the needle last longer in the human body environment. This design enables efficient delivery of more than 90% of the drug within 5 minutes of application of MNPs to the skin.<ref name="Li 2103359">{{Cite journal|last1=Li|first1=Song|last2=Xia|first2=Dengning|last3=Prausnitz|first3=Mark R.|date=2021-06-21|title=Efficient Drug Delivery into Skin Using a Biphasic Dissolvable Microneedle Patch with Water-Insoluble Backing|journal=Advanced Functional Materials|volume=31|issue=44|page=2103359|doi=10.1002/adfm.202103359|pmid=34744551 |pmc=8570388 |issn=1616-301X}}</ref> ==== 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.<ref name="Li 2103359"/> ==== 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 are the least popular because of the complex manufacturing and applying process.<ref name=":1" /> === Advantages === [[File:Medical waste sorting in hospital.jpg|thumb|Disposing needlestick might cause injuries and transmission of pathogen.<ref>{{Cite journal|last=Rosenkranz|first=Cora|date=2021|title=Netzwerk- und Energiemanagement in Rechenzentren|journal=Technische Sicherheit|volume=11|issue=1–02|pages=20–21|doi=10.37544/2191-0073-2021-01-02-20|s2cid=234172001 |issn=2191-0073}}</ref>]] # The MNPs may puncture the skin surface, enabling rapid onset of drug bypassing directly into the dermal capillaries.<ref name=":2"/> # Pain-free. # Can be localized to provide direct access to the intended tissues.<ref name=":2" /> # Less dependent on skilled medical workers, as MNPs can be administered safely by the patient themself.<ref name=":2" /> # 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.<ref name="Kearney 605">{{Cite journal|last1=Kearney|first1=Mary-Carmel|last2=McKenna|first2=Peter E.|last3=Quinn|first3=Helen L.|last4=Courtenay|first4=Aaron J.|last5=Larrañeta|first5=Eneko|last6=Donnelly|first6=Ryan F.|date=2019-11-13|title=Design and Development of Liquid Drug Reservoirs for Microneedle Delivery of Poorly Soluble Drug Molecules|journal=Pharmaceutics|volume=11|issue=11|page=605|doi=10.3390/pharmaceutics11110605|pmid=31766145 |pmc=6920785|issn=1999-4923|doi-access=free }}</ref> # Better safety compared to needle and syringe method (needlestick). Less waste, eliminate pathogen transmission, and injuries. At least 300,000 needlestick related injuries occurred in the US annually, with disposal contribute to almost half of the injuries.<ref name="Kearney 605"/> === Application === ==== MNPs as vaccine delivery platform ==== [[File:ZOSTAVAX (shingles (herpes zoster) vaccine (live)) (United Kingdom).jpg|thumb|A set of conventional vaccine apparatus needed to be transported.<ref>{{Cite web|title=Home - electronic medicines compendium (emc)|url=https://www.medicines.org.uk/emc|access-date=2021-11-22|website=www.medicines.org.uk}}</ref>]] 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, [[Mark Prausnitz]], co-developer of the 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.<ref name=":3">{{Cite web|last=CDC|date=2021-11-19|title=CDC Works 24/7|url=https://www.cdc.gov/index.htm|access-date=2021-11-22|website=Centers for Disease Control and Prevention|language=en-us}}</ref> Medical waste such as syringes and dirty needles are also eliminated, reducing the possibility of pathogen transmission of blood-borne disease in rural areas.<ref name="dx.doi.org"/> 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<ref name=":3" /> ==== MNPs for cosmetic and skin care ==== Skin treatment including face whitening agent and dark eye circles serum can also incorporated in MNPs.<ref>{{Cite journal|last1=Park|first1=Kui Young|last2=Kwon|first2=Hyun Jung|last3=Youn|first3=Choon Shik|last4=Seo|first4=Seong Jun|last5=Kim|first5=Myeong Nam|date=2018|title=Treatments of Infra-Orbital Dark Circles by Various Etiologies|journal=Annals of Dermatology|volume=30|issue=5|pages=522–528|doi=10.5021/ad.2018.30.5.522|pmid=33911473 |pmc=7992473 |issn=1013-9087}}</ref> 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.<ref>{{Cite journal|last1=Park|first1=Kui Young|last2=Kwon|first2=Hyun Jung|last3=Lee|first3=Changjin|last4=Kim|first4=Daegun|last5=Yoon|first5=Jun Jin|last6=Kim|first6=Myeong Nam|last7=Kim|first7=Beom Joon|date=2017-06-02|title=Efficacy and safety of a new microneedle patch for skin brightening: A Randomized, split-face, single-blind study|journal=Journal of Cosmetic Dermatology|volume=16|issue=3|pages=382–387|doi=10.1111/jocd.12354|pmid=28574158 |s2cid=19414988 |issn=1473-2130}}</ref> === Safety === MNPs may cause skin irritation on people with sensitive skin. Majority of studies show that MNPs do not irritate the skin. Especially for hollow MNPs, the not so stiff needles may cause unnecessary puncture of the skin outer layer, and may cause trauma to the skin and restricting the performance and flow of the drugs to the body.<ref name=":1" /> === 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.
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