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Microneedles (MNs) are medical tools used for microneedling, primarily in drug delivery, disease diagnosis, and collagen induction therapy. Known for their minimally invasive and precise nature, MNs consist of arrays of micro-sized needles ranging from 25μm to 2000μm. Although the concept of microneedling was first introduced in the 1970s, its popularity has surged due to its effectiveness in drug delivery and its cosmetic benefits.
Since the 2000s, there has been discoveries on new fabrication materials of MNs, like silicon, metal and polymer. Alongside with materials, a variety of MNs types (solid, hollow, coated, hydrogel) has also been developed to possess different functions. The research on MNs has led to improvements in different aspects, including instruments and techniques, yet adverse events are possible in MNs users.
History
editThe concept of microneedles was first derived from the use of large hypodermic needles in the 1970s,[1] but it only became prominent in the 1990s as microfabrication manufacturing technology developed.[1] Later, the concept of MNs finally came into experimentation in 1994 when Orentreich discovered the insertion of tri-beveled needles to the skin could possibly stimulates the release of fibrous strand.[1][2] The investigation on MNs’ potential to improve transdermal drug delivery gradually raised public awareness of MNs.[1] Since then, there has been massive research conducted on MNs, contributing to the development of different materials, types, and fabrication methods of MNs. Application and adverse events are explored.[3] In the 2000s, clinical trials on MNs’ use in drug delivery began.[3]
Materials of microneedles
editMicroneedles (MNs) consist of micro-sized needles arrays that are made of various materials exhibiting different characteristics and are suitable in the synthesis of different types of MNs. The selection of materials for formation of MNs greatly depends on the strength of skin penetration, manufacturing method, and rate of drug release.[3]
Silicon is the first material used for the production of MNs.[3] While the flexible nature of silicon allows easy manufacture of different sizes and types of MNs, silicon MNs can easily fracture during insertion in the skin.[4] On the contrary, MNs made of metals like stainless steel, titanium, and aluminum, are non-toxic and possess strong mechanical properties to penetrate the skin without breakage.[3][4] Nevertheless, metal MNs may cause allergic effects in some patients and it creates non-biodegradable wastes.[4][5]
Polymer is also regarded as a promising material for MNs due to its good biocompatibility and low toxicity.[3][4] Water-soluble polymers are more commonly used within the big polymer group and MNs tip breaking is more likely compared to MNs made of silicon and metal.[3][4] Therefore, polymer is a more suitable material for dissolving MNs or hydrogel-forming MNs.
Types of microneedles
editMicro-sized needles in a microneedles (MNs) device can be as short as 25μm or even 2000μm in length depending on their types.[3] There are mainly five types of microneedles (MNs): Solid, hollow, coated, dissolving, and hydrogel. The distinct characteristic of each type of MNs allow a variety of clinical applications, including diagnosis and treatment.[3]
Solid microneedles
editSolid MNs are the first type of MNs fabricated and are the most commonly used.[6] Hard solid MNs have sharp tips that pierce through and form pores on the stratum corneum.[3][6] A drug patch will then be applied to the skin for drug to be absorbed slowly and passively through numerous micropores.[6]
Solid MNs help increase the permeability and absorption of drugs.[6]
Hollow microneedles
editHollow MNs are designed with a hole at the tip and a hollow capacity that store drugs.[6] Upon MNs insertion, stored drug is directly injected into the dermis and this effectively facilitates the absorption of either large-molecular or large-dosage drug.[3][6] Yet, a portion of the drug can be leaked or clogged and it may hinders the overall drug administration.[3]
Coated microneedles
editCoated MNs are fabricated by coating drug solution over solid MNs and the thickness of the drug layer can be adjusted depending on the amount of drug to be administered.[3][7] A benefit of coated MNs is that less amount of drug is needed as compared to other drug administration route.[3][6][7] This is because the layer of drug will quickly dissolve and delivered into the systemic circulation directly across the skin.[6][7] The solid MNs which are removed afterwards may be contaminated by left-over drugs and the reuse of those MNs raise the concern of cross-infection between patients.[3][7]
Dissolving microneedles
editDissolving MNs are mostly composed of water-soluble drugs that enable the dissolution of MN tips when inserted into skin.[3][7] This is a one-step approach which does not require the removal of MNs and is convenient for long-term therapy.[3][6] However, incomplete insertion and delay dissolution is observed with the use of dissolving MNs.[6]
Hydrogel-forming microneedles
editThe primary material for the fabrication of hydrogel-forming microneedles (HFMs) is hydrophilic polymer that encloses drugs.[6][8] This material draws water from interstitial fluid in the stratum corneum and results in polymer swelling and release of drug.[6][8] Besides, the hydrophilic features of HFMs allow readily uptake of interstitial fluid that could be used for disease diagnosis.[8]
Application and principle
editTransdermal drug delivery
editThe most abundant transdermal drug administration route currently is via hypodermic needles, transdermal patches, and topical creams.[6] However, these routes have limited therapeutic effects because stratum corneum serves as a barrier that reduces the entry of drug molecules into the systemic circulation and target tissues.[6] The invention of MNs have retained the benefits of both hypodermic needles and transdermal patches while minimizing their cons.[3][9]
Compared to hypodermic needles, MNs provide a pain-free administration.[2][3] MNs are able to penetrate through the epidermis, but not any deeper to compress on nerve-ends to produce pain responses.[2][3] The superficial penetration also lessen the infection risk.[10]
Compared to transdermal patches, MNs are proven to be effective in producing micropores on the epidermis. The micropores facilitate the absorption of large molecules, like calcein and insulin, by 4 times via in-vitro skin models.[2] In addition, MNs' direct drug delivery to systemic circulation avoided the first-pass effect in the liver.[10] Significantly increasing the drug bioavailability, and the fast absorption into the systemic circulation also allowed a fast onset of action. Therefore, MNs could benefit diabetes treatment as common oral delivery would lead to a significant loss of insulin from degradation in the liver (first-pass effect) and insulin molecules are too large to be absorbed using common transdermal patches.[10]
Furthermore, the high precision of MNs also allows drug reaching to localized tissues precisely, for instance, intradermal layers for cancer or the eye for ophthalmic disorder.[9]
Vaccination
editMNs are suitable for vaccination with their capability to deliver macromolecules and maintain a slow and sustained release of vaccine agents by using both coated and dissolving MNs.[9] In addition, MNs' biodegradability minimizes biohazardous waste, unlike hypodermic needles.[3][9] The application of MNs in vaccination would benefit people who avoid vaccination due to trypanophobia (fear of needles in medical settings).[9]As of 2024, it has been found to generate an immune response similar to injection of measles and rubella vaccine.[11]
Disease diagnosis and monitoring
editDisease diagnosis and monitoring of therapeutic efficacy is possible by detecting several biomarkers in body fluid. However, current tissue fluid extraction methods are pain-inducing, and it may take up to hours or days for samples to be analyzed in medical laboratories.[3] MNs could collect body fluid in an almost painless manner, and it could provide immediate diagnosis when combined with a sensor.
MNs allow penetration through the epidermis but not long enough to compress nerves in deeper layers, and thus, they are minimally invasive and almost painless. MNs' precision also allow the extraction of fluid surrounding diseased tissues, which may contain higher concentration of different biomarkers and specific biomarkers that are not present in the systemic circulation.[12] These fluids provide more clinically significant and accurate values than those extracted from the systemic circulation, subsequently lowering the chances of underestimation of disease severity, especially for localized diseases.[12]
Furthermore, MNs are capable of providing (near) real-time diagnosis, and it is easily administrated with simple procedures.[13] Thus, MNs are potential candidates for Point-of-care (PoC) testing which could be conducted bedside.[13]
Hollow MNs and hydrogel MNs could be used to diagnose and monitor several diseases including Cataracts, Diabetes, Cancer, and Alzheimer’s disease.[3][12] For instance, hollow glass MNs and hydrogel MNs could extract skin interstitial fluid for the detection of glucose levels.[3][12]
Collagen induction therapy
editIn the field of dermatology, MNs are more commonly known as collagen induction therapy. The therapy induces dermis regeneration via repetitive perforation of the skin using sterilized MNs.[14] The repetitive penetration through the stratum corneum forms micropores, and these physical traumas to the skin sequentially stimulate the wound-healing cascade and expression of collagen and elastin in the dermis.[14]
By making use of the human natural regeneration properties, microneedling could be used alone to treat scars, wrinkles, and skin rejuvenation, or in combination therapy with topical tretinoin and vitamin C for enhanced effect.[2][14] Recent research has expanded the possibilities of MNs to treat pigmentation disorder, actinic keratosis, and promote hair growth in patients of androgenetic alopecia and alopecia areata.[2][14][15]
MNs have been diverged into different forms, including Dermapen and Dermarollers. Dermarollers are hand-held rollers equipped with a total of 192 solid steel micro-sized needles arranged into 24 arrays, lengths ranging from 0.5-1.5mm.[14][16] With the growing popularity of microneedling, MNs have also been commodified into home care Dermarollers, which are similar to medical dermarollers, except that the needles are shorter (0.15mm).[16] This is a more budget-friendly device that allows individuals to perform microneedling at home.
Safety profile
editApart from procedural pain, some common post-treatment adverse events (AEs) of MNs include temporary discomfort, erythema (skin redness), and edema.[2][17] Pinpoint bleeding, itching, irritation, and bruising are also possible in some cases.[2][17] However, most of the adverse side effects are not long-lasting and could be resolved spontaneously within 24 hours after the treatment, making MNs a rather safe tool.[17][18] Photoprotection and minimal exposure to chemicals irritants are often advised for an effective recovery and lowered chance of skin inflammation.[17]
Severe risks may be possible if there are technical errors during the procedure. For example, the usage of non-sterile tools might result in post-inflammatory hyperpigmentation, systemic hypersensitivity, local infections, etc.[2] Moreover, if excess pressure is used over a bony prominence, it could lead to “Tram-track scarring”.[17] But this could be avoided by using smaller needles and prevent over-pressurizing on top of these areas.[17] In addition, if the patient is allergic to the either the drug used or the material of MNs, contact dermatitis is possible.[2] Therefore, clinicians should be cautious towards patients with high risks of allergy.[18]
References
edit- ^ a b c d Tucak, Amina; Sirbubalo, Merima; Hindija, Lamija; Rahić, Ognjenka; Hadžiabdić, Jasmina; Muhamedagić, Kenan; Čekić, Ahmet; Vranić, Edina (2020-10-27). "Microneedles: Characteristics, Materials, Production Methods and Commercial Development". Micromachines. 11 (11): 961. doi:10.3390/mi11110961. ISSN 2072-666X. PMC 7694032. PMID 33121041.
- ^ a b c d e f g h i j Singh, Aashim; Yadav, Savita (2016). "Microneedling: Advances and widening horizons". Indian Dermatology Online Journal. 7 (4): 244–254. doi:10.4103/2229-5178.185468. ISSN 2229-5178. PMC 4976400. PMID 27559496.
- ^ a b c d e f g h i j k l m n o p q r s t u v w x Aldawood, Faisal Khaled; Andar, Abhay; Desai, Salil (2021). "A Comprehensive Review of Microneedles: Types, Materials, Processes, Characterizations and Applications". Polymers. 13 (16): 2815. doi:10.3390/polym13162815. ISSN 2073-4360. PMC 8400269. PMID 34451353.
- ^ a b c d e Ma, Guojun Ma; Wu, Chengwei (2017-04-10). "Microneedle, bio-microneedle and bio-inspired microneedle: A review". Journal of Controlled Release. 251: 11–23. doi:10.1016/j.jconrel.2017.02.011. PMID 28215667. Retrieved 2024-03-27.
- ^ Luo, Xiaojin; Yang, Li; Cui, Yue (2023-06-06). "Microneedles: materials, fabrication, and biomedical applications". Biomedical Microdevices. 25 (3): 20. doi:10.1007/s10544-023-00658-y. ISSN 1572-8781. PMC 10242236. PMID 37278852.
- ^ a b c d e f g h i j k l m n Waghule, Tejashree; Singhvi, Gautam; Dubey, Sunil Kumar; Pandey, Murali Monohar; Gupta, Gaurav; Singh, Mahaveer; Dua, Kamal (2019-01-01). "Microneedles: A smart approach and increasing potential for transdermal drug delivery system". Biomedicine & Pharmacotherapy. 109: 1249–1258. doi:10.1016/j.biopha.2018.10.078. ISSN 0753-3322. PMID 30551375.
- ^ a b c d e Kwon, Ki Mun; Lim, Su-Min; Choi, Seulgi; Kim, Da-Hee; Jin, Hee-Eun; Jee, Grace; Hong, Kee-Jong; Kim, Joo Young (2017-07-01). "Microneedles: quick and easy delivery methods of vaccines". Clinical and Experimental Vaccine Research. 6 (2): 156–159. doi:10.7774/cevr.2017.6.2.156. ISSN 2287-3651. PMC 5540964. PMID 28775980.
- ^ a b c Turner, Joseph G.; White, Leah R.; Estrela, Pedro; Leese, Hannah S. (2021). "Hydrogel-Forming Microneedles: Current Advancements and Future Trends". Macromolecular Bioscience. 21 (2): e2000307. doi:10.1002/mabi.202000307. ISSN 1616-5187. PMID 33241641.
- ^ a b c d e Menon, Ipshita; Bagwe, Priyal; Gomes, Keegan Braz; Bajaj, Lotika; Gala, Rikhav; Uddin, Mohammad N.; D’Souza, Martin J.; Zughaier, Susu M. (2021-04-14). "Microneedles: A New Generation Vaccine Delivery System". Micromachines. 12 (4): 435. doi:10.3390/mi12040435. ISSN 2072-666X. PMC 8070939. PMID 33919925.
- ^ a b c Amarnani, Ragini; Shende, Pravin (2022). "Microneedles in diagnostic, treatment and theranostics: An advancement in minimally-invasive delivery system". Biomedical Microdevices. 24 (1): 4. doi:10.1007/s10544-021-00604-w. ISSN 1387-2176. PMC 8651504. PMID 34878589.
- ^ Harris, Emily (2024-05-24). "Microneedle Vaccine Patches Generated Immune Response in Children". JAMA. doi:10.1001/jama.2024.8629. ISSN 0098-7484.
- ^ a b c d Himawan, Achmad; Vora, Lalitkumar K.; Permana, Andi Dian; Sudir, Sumarheni; Nurdin, Airin R.; Nislawati, Ririn; Hasyim, Rafikah; Scott, Christopher J.; Donnelly, Ryan F. (2023). "Where Microneedle Meets Biomarkers: Futuristic Application for Diagnosing and Monitoring Localized External Organ Diseases". Advanced Healthcare Materials. 12 (5): e2202066. doi:10.1002/adhm.202202066. ISSN 2192-2640. PMID 36414019.
- ^ a b Dixon, Rachael V.; Skaria, Eldhose; Lau, Wing Man; Manning, Philip; Birch-Machin, Mark A.; Moghimi, S. Moein; Ng, Keng Wooi (2021-08-01). "Microneedle-based devices for point-of-care infectious disease diagnostics". Acta Pharmaceutica Sinica B. Hot Topic Reviews in Drug Delivery. 11 (8): 2344–2361. doi:10.1016/j.apsb.2021.02.010. ISSN 2211-3835. PMC 8206489. PMID 34150486.
- ^ a b c d e Iriarte, Christopher; Awosika, Olabola; Rengifo-Pardo, Monica; Ehrlich, Alison (2017-08-08). "Review of applications of microneedling in dermatology". Clinical, Cosmetic and Investigational Dermatology. 10: 289–298. doi:10.2147/CCID.S142450. PMC 5556180. PMID 28848356.
- ^ Clinics, Dr Tetiana MamontovaHair Transplant Surgeon at Harley Street Hair Transplant; surgeons, GMC registered doctor One of our most experienced hair restoration; ISHRS, a member of the gold standard medical association (2023-06-06). "Microneedling For Hair Loss: Does It Actually Work? - Harley Street HTC". www.harleystreethairtransplant.co.uk. Retrieved 2024-03-27.
- ^ a b Doddaballapur, Satish (2009). "Microneedling with Dermaroller". Journal of Cutaneous and Aesthetic Surgery. 2 (2): 110–111. doi:10.4103/0974-2077.58529. ISSN 0974-2077. PMC 2918341. PMID 20808602.
- ^ a b c d e f Gowda, Asha; Healey, Brayden; Ezaldein, Harib; Merati, Miesha (2021). "A Systematic Review Examining the Potential Adverse Effects of Microneedling". The Journal of Clinical and Aesthetic Dermatology. 14 (1): 45–54. ISSN 1941-2789. PMC 7869810. PMID 33584968.
- ^ a b Chu, Sherman; Foulad, Delila P.; Atanaskova Mesinkovska, Natasha (2021). "Safety Profile for Microneedling: A Systematic Review". Dermatologic Surgery. 47 (9): 1249–1254. doi:10.1097/01.DSS.0000790428.70373.f6. ISSN 1076-0512. PMID 34448760.