Microneedles for Skin Vaccination

Main Article Content

Boonnada Pamornpathomkul
Nattawat Natpoolwat
Tanasait Ngawhirunpat


Vaccination represents the best method for prevention from infectious diseases. An ideal vaccine is safe, minimally invasive administered and induce a strong protective immune response. The traditional administration of vaccines via hypodermic needle can be painful and cause stress, especially in needle phobic patient. Professional healthcare personnel are needed for the administration of vaccines, and these persons are at high risk of needlestick injuries. Moreover, sharps waste disposal and the reuse of needles are both considerable problems. Skin immunization is a promising alternative to administration of vaccines via the intramuscular and subcutaneous routes. The skin is an attractive organ for vaccination, which target the high density of immunologic antigen-presenting cells residing both within the epidermis and dermis include Langerhans cells and dermal dendritic cells, respectively. However, the formidable barrier properties of the uppermost layer of the skin, the stratum corneum, act as a major challenge for successful delivery of vaccine into the skin. The strategy of microneedle involves breach the stratum corneum barrier in order to enable delivery of vaccine through the skin. MNs are microns-sized needles and lengths up to 1 mm. The main advantages of MNs are minimally invasive, mostly pain-free, easy to use, large scale production, and inexpensive cost. Many published studies suggest that vaccination in the skin using a microneedle technique provides improve protective immunity, and simplify for skin vaccination. In this review, we briefly summarized the use of microneedles for the delivery of vaccines and provided examples of its application for skin vaccination. Finally, we give our view on research about safety of the microneedles that is needed to provide microneedle for skin vaccination clinically useful in the near future.


Download data is not yet available.

Article Details

Review Article


Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. Philadelphia (PA): Elsevier Saunders; 2012.

Adams D, Quayum M, Worthington T, et al. Evaluation of a 2% chlorhexidine gluconate in 70% isopropyl alcohol skin disinfectant. J Hosp Infect 2005;61:287-90.

Bal SM, Caussin J, Pavel S, et al. In vivo assessment of safety of microneedle arrays in human skin. Eur J Pharm Sci 2008;35(3):193-202.

Bal SM, Ding Z, van Riet E, et al. Advances in transcutaneous vaccine delivery: do all ways lead to Rome? J Control Release 2010; 148(3): 266-82.

Bal SM, Slutter B, Jiskoot W, et al. Small is beautiful: N-trimethyl chitosan-ovalbumin conjugates for microneedle-based transcutaneous immunization. Vaccine 2011; 29(23): 4025-32.

Barker JH, Ryan TJ. Skin microcirculation In: Barker JH, Anderson GL, Menger MD, editors. Clinically applied microcirculation research. CRC, Boca Raton, Florida; 1995: 315-38.

Bauer D, Grebe R, Ehrlacher A. A new method to model change in cutaneous blood flow due to mechanical skin irritation part I: comparison between experimental and numerical data. J Theor Biol 2006; 238(3): 575-87.

Pamornpathomkul B, Ngawhirunpat T. Microneedle techniques for DNA transdermal delivery. IJPS 2015; 11(2): 16-30.

Casado I, Martínez-Baz I, Floristán Y, et al. Cause of death in hospitalized patients with laboratory-confi rmed infl uenza. An Sist Sanit Navar 2015; 38(2): 263-268.

Centers for Disease Control and Prevention. Epidemiology and prevention of vaccinepreventable diseases. The Pink Book: Course Textbook - 13th Edition [serial online] 2015a [cited 2015 Jun 17]. Available from: URL:http:// www.cdc.gov/vaccines/pubs/pinkbook/vac-admin.html#route

Centers for Disease Control and Prevention. Epidemiology and prevention of vaccinepreventable diseases. The Pink Book: Course Textbook - 13th Edition [serial online] 2015b [cited 2015 Jun 17]. Available from: URL:http://www.cdc.gov/vaccines/pubs/pinkbook/prinvac.html

Chew AL, Maibach HI. Irritant Dermatitis. Springer; 2006.

Choi HJ, Bondy BJ, Yoo DG, et al. Stability of whole inactivated infl uenza virus vaccine during coating onto metal microneedles. J Control Release 2013; 166(2): 159-71.

Cook IF. Evidence based route of administration of vaccines. Hum Vaccin 2008; 4(1): 67-73.

Cormier M, Daddona PE. Macrofl ux technology for transdermal delivery of therapeutic proteins and vaccines. In: Rathbone MJ, Hadgraft J, Roberts MS, editors. Modifi edrelease drug delivery technology. Marcel Dekker: USA; 2003. 589-98.

Cormier M, Johnson B, Ameri M, et al. Transdermal delivery of desmopressin using a coated microneedle array patch system. J Control Release 2004; 97(3): 503-11.

Corsini E, Galli CL. Cytokines and irritant contact dermatitis. Toxicol Lett 1998; 102-103: 277-82.

Corsini E, Galli CL. Epidermal cytokines in experimental contact dermatitis. Toxicology 2000; 142(3): 203-11.

Davis R, Biellik R. Inactivated polio vaccine: its proposed role in the fi nal stages of polio eradication. Pan Afr Med J 2013; 14: 102.

De Jongh CM, Verberk MM, Withagen CE, et al. Stratum corneum cytokines and skin irritation response to sodium lauryl sulfate. Contact dermatitis 2006; 54(6): 325-33.

Dowdle W. The principles of disease elimination and eradication. Bull World Health Organ 1998; 76(Suppl. 2): 23-5.

Draelos ZD and Pugliese PT. Physiology of the skin. Carol Stream: Allured Pub Corp, USA; 2011.

Edens C, Dybdahl-Sissoko NC, Weldon WC, et al. Inactivated polio vaccination using a microneedle patch is immunogenic in the rhesus macaque. Vaccine 2015; 33:4683-90.

Fluhr JW, Akengin A, Bornkessel A, et al. Additive impairment of the barrier function by mechanical irritation, occlusion and sodium lauryl sulphate in vivo. Br J Dermatol 2005; 153(1): 125-31.

Gill HS, Denson DD, Burris BA, et al. Effect of microneedle design on pain in human volunteers. Clin J Pain 2008; 24(7): 585-9.

Gill HS, Prausnitz MR. Coated microneedles for transdermal delivery. J Control Release 2007; 117(2): 227-237.

Gupta J, Park SS, Bondy B, Felner EI, Prausnitz MR. Infusion pressure and pain during microneedle injection into skin of human subjects. Biomaterials 2011;32(28): 6823-31.

Haq MI, Smith E, John DN, et al. Clinical administration of microneedles: skin puncture, pain and sensation. Biomed Microdevices 2009; 11(1):35-47.

Heymann DL, Aylward LB. Perspective-Global health: eradicating polio. N Engl J Med 2004; 351: 1275-7.

Hirobe S, Azukizawa H, Hanafusa T, et al. Clinical study and stability assessment of a novel transcutaneous infl uenza vaccination using a dissolving microneedle patch. Biomaterials 2015; 57: 50-8.

Indermun S, Luttge R, Choonara YE, et al. Current advances in the fabrication of microneedles for transdermal delivery. J Control Release 2014; 185(0): 130-8.

Jhawat VC, Saini V, Kamboj S, et al. Transdermal drug delivery systems: approaches and advancements in drug absorption through skin. Int J Pharm Sci Rev Res 2013; 20(1): 47-56.

Kanitakis J. Anatomy, histology and immunohistochemistry of normal human skin. Eur J Dermatol 2002; 12(4): 390-9; quiz 400-1.

Kim YC, Quan FS, Yoo DG, et al. Improved infl uenza vaccination in the skin using vaccine coated microneedles. Vaccine 2009; 27(49): 6932-8.

Kim YC, Suh H, Shin J. Microneedle patches for vaccine delivery. Clin Exp Vaccine Res 2014;3(1):42-9.

Kis EE, Winter G, Myschik J. Devices for intradermal vaccination. Vaccine 2012; 30(3): 523-38.

Kock A, Schwarz T, Kirnbauer R, et al. Human keratinocytes are a source for tumor necrosis factor alpha: evidence for synthesis and release upon stimulation with endotoxin or ultraviolet light. J Exp Med 1990; 172(6): 1609-14.

Lever WF and Schaumburg-Lever G. Histopathology of the skin. Philadelphia: J. B. Lippincott; 1983.

Levine MM. Can needle-free administration of vaccines become the norm in global immunization? Nat Med 2003; 9(1): 99-103.

Levinson W. Review of medical microbiology and immunology. New York: McGraw-Hill Medical; 2010.

Levin Y, Kochba E, Kenney R. Clinical evaluation of a novel microneedle device for intradermal delivery of an infl uenza vaccine: are all delivery methods the same? Vaccine 2014; 32(34): 4249-52.

Lydyard P, Whelan A, Fanger M. Immunology. New York: Garland Science; 2011.

Matriano JA, Cormier M, Johnson J, et al. Macrofl ux microprojection array patch technology: a new and effi cient approach for intracutaneous immunization. Pharm Res 2002; 19(1): 63-70.

McCrudden MTC, McAlister E, Courtenay AJ, et al. Microneedle applications in improving skin appearance. Exp Dermatol 2015: 24:561-6.

Naito S, Ito Y, Kiyohara T, et al. Antigen-loaded dissolving microneedle array as a novel tool for percutaneous vaccination. Vaccine 2012; 30(6): 1191-7.

National Institute of Allergy and Infectious Diseases. Understanding vaccines What they are how they work [serial online] 2008 [cited 2015 Jun 17]. Available from: URL: http://www.niaid.nih.gov/topics/vaccines/


Owen JA, Punt J, Stranford SA. Kuby immunology. New York: W. H. Freeman & Company; 2013.

Peakman M, Vergani D. Basic and clinical immunology. New York: Churchill Livingstone/Elsevier; 2009.

Prausnitz M, Mikszta J, Cormier M, et al. Microneedle-Based Vaccines. In: Compans RW, Orenstein WA, editors. Vaccines for Pandemic Infl uenza. Current Topics in Microbiology and Immunology. Springer

Berlin Heidelberg, Germany; 2009. 369-93.

Romani N, Holzmann S, Tripp CH, et al. Langerhans cells – dendritic cells of the epidermis. APMIS 2003; 111(7-8): 725-40.

Sandby-Moller J, Poulsen T, Wulf HC. Epidermal thickness at different body sites: relationship to age, gender, pigmentation, blood content, skin type and smoking habits. Acta Derm Venereol 2003; 83(6): 410-3.

Sparber F, Tripp CH, Hermann M, et al. Langerhans cells and dermal dendritic cells capture protein antigens in the skin: Possible targets for vaccination through the skin. Immunobiology 2010; 215: 770-9.

Tuan-Mahmood TM, McCrudden MTC, Torrisi BM, et al. Microneedles for intradermal and transdermal drug delivery. Eur J Pharm Sci 2013; 50(5): 623-37.

van der Maaden K, Jiskoot W, Bouwstra J. Microneedle technologies for (trans)dermal drug and vaccine delivery. J Control Release 2012; 161(2): 645-55.

van der Maaden K, Sekerdag E, Jiskoot W, Bouwstra J. Impact-insertion applicator improves reliability of skin penetration by solid microneedle arrays. AAPS J 2014a; 16(4): 681-4.