Review of Microneedle based Transdermal Drug Delivery Systems

DOI:

https://doi.org/10.37285/ijpsn.2019.12.3.1

Authors

  • Rabinarayan Parhi
  • Divya Supriya N

Abstract

Transdermal drug delivery (TDD) provides an attractive and alternative drug delivery when compared to oral and other drug delivery as the former route offers several advantages like avoiding pre-systemic first pass metabolism of administered drugs, patient compliance, and avoiding gastric irritation. However, stratum corneum (SC), the upper most layer of skin, limits the permeation of number of drugs because of its barrier property. To breach or bypass this barrier, two approaches namely: chemical and physical are generally used. Physical approaches seem to be better as it does not involve the use of chemicals in the formulations, which could interact, with other component of formulations and more importantly may cause reversible damage to the skin. Microneedle technique is one of the most advanced physical techniques, which can easily by-pass, the SC and allow the drug to reach viable epidermis directly. The needles used in microneedle techniques are in hundreds of micron length range and when applied on skin generally produce little or no pain. The objective of this review is mainly focused on types of microneedles, various materials and fabrication techniques used in the preparation of microneedles. Furthermore, various techniques used in the application of microneedles and mechanism of action are described. In addition, this review also describes commercial products, patents on microneedle technology and recent works carried out on microneedles research and safety aspects of microneedles.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Keywords:

Microneedles, Hydrogel-forming, Two-photon polymerization, Micromolding process

Downloads

Published

2019-05-31

How to Cite

1.
Parhi R, N DS. Review of Microneedle based Transdermal Drug Delivery Systems. Scopus Indexed [Internet]. 2019 May 31 [cited 2024 Nov. 19];12(3):4511-23. Available from: https://ijpsnonline.com/index.php/ijpsn/article/view/297

Issue

Section

Review Articles

References

Aggarwal P and Johnston CR (2004). Geometrical effects in mechanical characterizing of microneedle for biomedical applications. Sensors & Actuators B 102: 226-34.
Al-Zahrani S, Zaric M, McCrudden C, Scott C, Kissenpfennig A and Donnelly RF (2012). Expert Opin. Drug Deliv 9: 541-50.
Arya J, Henry S, Kalluri H, McAllister DV, Pewin WP and Prausnitz MR (2017). Tolerability, usability and acceptability of dissolving microneedle patch administration in human subjects. Biomaterials 128: 1-7.
Banga AK (2009). Microporation applications for enhancing drug delivery. Expert Opin. Drug Deliv 6: 343-354.
Banks D (2006). Microengineering, MEMS, and Interfacing: A Practical Guide, 1st ed.Boca Raton.
Bariya SH, Gohel MC, Mehta TA and Sharma OP (2012). Microneedles: An emerging transdermal drug delivery system: Royal Pharmaceutical Society. Journal of Pharmacy and Pharmacology 64: 11-29.
Birchall JC (2006). Microneedle array technology : The time is right but is the science ready? Expert Rev Med Devices 3: 1-4.
Brogden NK, Banks SL, Crofford LJ and Stinchcomb AL (2013). Diclofenac enables unprecedented week-long microneedle-enhanced delivery of a skin impermeable medication in humans. Pharm. Res 30: 1947-1955.
Burton SA, Ng CY, Simmers R, Moeckly C, Brandwein D, Gilbert T, Johnson N, Brown K, Alston T and Prochnow G (2011). Rapid intradermal delivery of liquid formulations using a hollow microstructured array. Pharm. Res 28: 31-40.
Bystrova S and Luttge R (2011). Micromolding for ceramic microneedle arrays. Microelectron.Eng 88: 1681-1684.
Cai B, Xia W, Bredenberg S and Engqvist H(2014). Self-setting bioceramic microscopic protrusions for transdermal drug delivery. J.Mater.chem.B2 2: 5992-5998.
Cao Y, Kakar P, Hossen Md N, Mei XW and Chen X (2017). Sustained epidermal powder drug delivery via skin microchannels. Journal of Controlled Release 249: 94-102.
Chandrasekaran S and Frazier AB (2003). Characterization of surface micromachined metallic microneedles. Journal of Microelectromechanical Systems 12: 289-295.
Chandrasekaran S, Brazzle JD and Frazier AB (2003). Surface micromachined metallic microneedles. Journal of Microelectro-mechanical Systems 12: 281-8.
Chaudhri BP, Ceyssens F, De Moor P, Hoof CV and Puers R (2010). A high aspect ratio SU-8 fabrication technique for hollow microneedles for transdermal drug delivery and blood extraction. J. Micromech. Microeng 20: 064006.
Chege M, McConville A and Davis J (2017). Microneedle drug delivery systems: Appraising opportunities for improving safety and assessing areas of concern. Journal of Chemical Health and Safety 24: 6-14.
Chen J, Qiu Y, Zhang S, Yang G and Gao Y (2015). Controllable coating of microneedles for transdermal drug delivery. Drug Dev Ind Pharm 41: 415-422.
Chen J, Huang W, Huang Z, Liu S, Ye Y, Li Q and Huang M (2018). Fabrication of Tip-Dissolving Microneedles for Transdermal Drug Delivery of Meloxicam. AAPS PharmSciTech 19: 1141-1151.
Cheung K and Das DB (2014). Microneedles for drug delivery: Trends and progress. Drug Delivery 23: 1-17.
Cheung K, Han T and Das DB (2014). Effect of Force of Microneedle Insertion on the Permeability of Insulin in Skin. J. Diabetes Sci. Technol 8: 444-452.
Chowdhury D F H (2010). “Microneedle Transdermal Delivery Device”. Loughborough Patent US 2010042050, 18 February 2010.
Chu LY, Choi SO and Prausnitz MR (2010). Fabrication of dissolving polymer microneedles for controlled drug encapsulation and delivery: Bubble and pedestal microneedle designs. J. Pharm. Sci 99: 4228-4238.
Davidson A, Al-Qallaf B and Bhusan DD (2008). Transdermal drug delivery by coated microneedles: geometry effects on effective skin thickness and drug permeability. Chem Eng Res Design 86: 1196-206.
Davis SP, Landis BJ, Adams ZH, Allen MG and Prausnitz MR (2004). Insertion of microneedles into skin: measurement and prediction of insertion force and needle fracture force. Journal of Biomechanics 37: 1155-63.
Davis SP, Martanto W, Allen MG and Prausnitz MR (2005). Hollow metal microneedles for insulin delivery to diabetic rats. IEEE Transactions on Biomedical Engineering 52: 909 -915.
Donnelly RF, McCrudden MTC, Alkilani AZ, Larran˜eta E, McAlister E, Courtenay JA, Kearney MC, Singh TRR, McCarthy HO , Kett VL , Salvador EC , Zahrani SA and Woolfson AD (2014). Hydrogel-Forming Microneedles Prepared from ‘‘Super Swelling’’ Polymers Combined with Lyophilised Wafers for Transdermal Drug Delivery. PLoS One 9: e111547.
Donnelly F, Singh TRR and Woolfson AD (2010). Microneedle-based drug delivery systems: Microfabrication, drug delivery, and safety. Drug Deliv 17: 187-207.
Donnelly RF and Douroumis D (2015). Microneedles for drug and vaccine delivery and patient monitoring. Drug Deliv. Trans. Res 5: 311-312.
Donnelly RF, Moffatt K, Alkilani AZ, Vicente-Pérez EM, Barry J, McCrudden MT and Woolfson AD (2014a). Hydrogel-forming microneedle arrays can be effectively inserted in skin by self application: A pilot study centred on pharmacist intervention and a patient information leaflet. Pharm. Res 31: 1989-1999.
Donnelly RF, Mooney K, McCrudden MTC, Vicente-Pérez EM, Belaid L, González-Vázquez P, McElnay J and Woolfson AD (2014b). Hydrogel-forming microneedles increase in volume during swelling in skin, but skin barrier function recovery is unaffected. J Pharm Sci 103: 1478-86.
Donnelly RF, Morrow DI, Singh TRR, Migalska K, McCarron PA, O’Mahony C and Woolfson AD (2009). Processing difficulties and instability of carbohydrate maltose microneedle arrays. Drug Dev.Ind.Pharm 35: 1242-1254.
Donnelly RF, Singh TRR and Woolfson AD (2010). Microneedle-based drug delivery systems: microfabrication, drug delivery, and safety. Drug Deliv 17: 187-207.
Donnelly RF, Singh TRR, Alkilani AZ, McCrudden MTC, O’Neill S, O’Mahony C, Armstrong K McLoone N, Kole P and Woolfson AD (2013). Hydrogel-forming microneedle arrays exhibit anti-microbial properties: Potential for enhanced patient safety. Int. J. Pharm 451: 76-91.
Donnelly RF, Singh TRR, Garland MJ, Migalska K, Majithiya R, McCrudden CM and Woolfson AD (2012). Hydrogel-Forming Microneedle Arrays for Enhanced Transdermal Drug Delivery. Advanced Functional Materials 22: 4879-4890.
Donnelly RF, Singh TRR, Garland MJ, Migalska K, Majithiy R and McCrudden CM (2012). Hydrogel-forming microneedle arrays for enhanced transdermal drug delivery. Adv Funct Mater 22: 4879-90.
Donnelly RF, Singh TRR, Marrow DIJ and Woolfson AD (2012), Microneedle Mediated Transdermal and Intradermal drug delivery, Belfast, UK.
Doraiswamy A, Ovsianikov A, Gittard SD, MonteiroRiviere NA-R, Crombez R, Montalvo E, Shen W, Chichkov BN and Narayan RJ(2010). Fabrication of Microneedles Using Two Photon Polymerization for Transdermal Delivery of Nanomaterials. J.Nanosci.Nanotechnol 10: 6305-6312.
Elias PM (1988). Structure and function of the stratum corneum permeability barrier. Drug Dev. Res 13: 97-105.
Escobar-chavez JJ, Bonilla-Martínez D, Villegas-González MA, Molina-Trinidad E, Casas-Alancaster N and Revilla-Vázquez AL (2011). Microneedles: A Valuable Physical Enhancer to Increase Transdermal Drug Delivery. Journal of clinical pharmacology 51: 964-977.
Garland MJ, Migalska K, Tuan-Mahmood TM, Singh TRR, Majithija R, Caffarel-Salvador E, McCrudden CM, McCarthy HO, David WA and Donnelly RF(2012). Influence of skin model on in vitro performance of drug-loaded soluble microneedle arrays. Int. J. Pharm 434: 80-89.
Ghosh P, Brogden NK and Stinchcomb AL (2014). Fluvastatin as a Micropore Lifetime Enhancer for Sustained Delivery Across Microneedle‐Treated Skin. J. Pharm. Sci 103: 652.
Gill HS and Prausnitz MR (2007). Coated microneedles for transdermal delivery. J. Control. Release 117: 227-237.
Gill HS and Prausnitz MR (2007). Coating formulations for microneedles. Pharmaceutical Research 24: 1369-80.
Gill HS, Andrews SN, Sakthivel SK, Fedanov A, Williams IR, Garber DA, Priddy FH, Yellin S, Feinberg MB, Staprans SI and Prausnitz MR (2009). Selective removal of stratum corneum by microdermabrasion to increase skin permeability. Eur. J. Pharm. Sci 38: 95-103.
Gittard SD, Narayan RJ, Jin C, Ovsianikov A,Chichkov BN, MonteiroRiviere NA , Stafslien S and Chisholm B (2009). Pulsed laser deposition of antimicrobial silver coating on Ormocer® microneedles. International society for Biofabrication 1: 4.
Gupta J, Gill HS, Andrews SN and Prausnitz MR(2011). Kinetics of skin resealing after insertion of microneedles in human subjects. J. Control. Release 154: 148.
Han M, Kim DK, Kang SH, Yoon HR, Kim BY, Lee SS, Kim KD and Lee HG (2009). Improvement in antigen-delivery using fabrication of a grooves-embedded microneedle array. ActuatorB-Chem 137: 274-280.
Henry S, McAllister DV, Allen MG and Prausnitz MR (1998). Microfabricated microneedles: a novel approach to transdermal drug delivery. J Pharm Sci 87: 922-5.
Hondak, MotoiM and K. TakadaK, “Method for producing stamper for microneedle”. Kyoto Patent CA 2696810, JP 2011078618, WO 2011043086, AU 2010201434, KR 2011067009, EP 2343102 A1, 10 February 2011.
Hong X,Wei L,Wu F, Wu Z, Chen L, Liu Z and Yuan W (2013). Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine.Drug Des Dev.Ther 7: 945-952.
Hopcroft MA, Hong X, Wei L, Wu F, Wu Z, Chen L, Liu Z and Yuan W (2013). Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine. Drug Des Dev. Ther 7: 945-952.
Indermun S, Luttge R, Choonara YE, Kumar P, Du Toit LC, Modi G and Pillay V (2014). Current advances in the fabrication of microneedles for transdermal delivery.J.Control.Release 185: 130-138.
Ita KB (2014). Transdermal drug delivery: Progress and challenges. J. Drug Del. Sci. Tech 24: 245-250.
Ito Y, Hagiwara E, Saeki A, Sugioka N and Takada K (2006). Feasibility of microneedles for percutaneous absorption of insulin. Eur. J. pharm. Sci 29: 82-88.
Jacoby E, Jarrahian C, Hull HF and Zehrung D (2015). Opportunities and challenges in delivering influenza vaccine by microneedle patch. Vaccine 33: 4699-4704.
Kaur M, Ita KB, Popova IE, Parikh SJ and Bair DA (2014). Microneedle-assisted delivery of verapamil hydrochloride and amlodipine besylate. Eur. J. Pharm. Biopharm 86: 284-291.
Kaushik S, Hord AH, Denson DD, McAllister DV, Smitra S, Allen MG and Prausnitz MR (2001). Lack of pain associated with microfabricated microneedles. Anesth. Analg 92: 502-504.
Kim YC, Park JH and Prausnitz MR (2012). Microneedles for drug and vaccine delivery. Adv. Drug Deliv. Rev 64: 1547-1568.
Kim YC, Quan FS, Compans RW, Kang SM and Prausnitz MR (2010). Formulation of Microneedles Coated with Influenza Virus-like Particle Vaccine. AAPS Pharm Sci Tech 11: 1193-1201.
Kolli CS and Banga AK (2008). Characterization of solid maltose microneedles and their use for transdermal delivery. Pharm Res 25: 104-13.
Larran˜eta E, Lutton REM, Woolfson AD and Donnelly RF (2016). Microneedle arrays as transdermal and intradermal drug delivery systems: Materials science, manufacture and commercial development. Materials Science and Engineering R 104: 1-32.
Lee JW, Park JH and Prausnitz MR (2008). Dissolving microneedles for transdermal drug delivery. Biomaterials 29: 2113-2124.
Lee K, Lee HC, Lee DS and Jung H (2010). Drawing lithography: three-dimensional fabrication of an ultrahigh-aspect-ratio microneedle. Adv. Mater 22: 483-486.
Lee K, Lee CY and Jung H (2011). Dissolving microneedles for transdermal drug administration prepared by stepwise controlled drawing of maltose. Biomaterials 32:3134-3140.
Li G, Badkar A, Nema S, Kolli CS and Banga AK(2009). In vitro transdermal delivery of therapeutic antibodies using maltose microneedles. Int.J.Pharm 368:109-115.
Lim CY. The plastic microneedle strip. Singapore Patent WO 2013066262, 10 May 2013.
Lippmann JM, Geiger EJ and Pisano AP (2007). Polymer investment molding: Method for fabricating hollow, microscale parts. Sens.Actuator A-phys 134: 2-10.
Ma G and Wu C (2017). Microneedle, bio-microneedle and bio-inspired microneedle: A review. Journal of Controlled Release 251: 11-23.
Mahmood- Tuan TM, McCrudden MTC, Torrisi BM, McAlister E, Singh TRR and Donelly RF (2013). Microneedles for intradermal and transdermal drug delivery. European Journal of Pharmaceutical Sciences 50: 623- 637.
Mahony CO (2014). Structural characterization and in-vivo reliability evaluation of silicon microneedles.Biomedical Microdevices 16: 333-343.
McCrudden MTC, Alkilani AZ, McCrudden CM, McAlister E, McCarthy HO, Woolfson AD and Donnelly RF(2014). Design and physicochemical characterisation of novel dissolving polymeric microneedle arrays for transdermal delivery of high dose, low molecular weight drugs. J Control Release 180: 71-80.
McGrath MG, Vucen S, Vrdoljak A, Kelly A, OMahony C, Crean AM and Moore A (2013). Production of dissolvable microneedles using an atomised spray process: Effect of microneedle composition on skin penetration. Eur. J. Pharm. Sci 86: 200-11.
Migdadi EM, Aaron J, Tekko IA, McCrudden MTC, Kearney MC, McAlister E, McCarthy HO and Donnelly RF(2018).Hydrogel-forming microneedles enhance transdermal delivery of metformin hydrochloride. Journal of Controlled Release 285: 142-151.
Moga BJ, Chase KB and Smith GD. Drug delivery device. Madison Patent WO 2011084951, US 20110172645, 14 July 2011.
Moon SJ, Lee SS, Lee HS and Kwon TH (2005). Fabrication of microneedle array using LIGA and hot embossing process. Microsyst.Technol 11: 311-318.
More S, Ghadge T and Dhole S (2013). Microneedle: An advanced technique in transdermal drug delivery system. Asian J. Res. Pharm. Sci 3: 141-148.
Moreau WM (1988). Semiconductor lithography, 1st ed. Hopwell junction, New York press.
Nagaich U (2017). Microneedles-mediated drug and vaccine delivery. J Adv Pharm Technol Res 8: 1.
Nguyen J, Ita KB, Morra MJ and Popova IE (2016) . The Influence of Solid Microneedles on the Transdermal Delivery of Selected Antiepileptic Drugs. Pharmaceutics 8: 33.
Nguyen NT (2012). Fundamentals, Design and Fabrication, Micromixers, 2nd ed.Singapore.
Niinomi M and Nakai M (2011). Titanium-Based Biomaterials for Preventing Stress Shielding between Implant Devices and Bone. Int.j.Biomater 2011: 10.
Nix WO and Kenny TW (2010). What is the Young's Modulus of Silicon?.Microelectromech. Syst 19: 229-238.
Nordquist L, Roxhed N, Griss P and Stemme G (2007). Novel microneedle patches for active insulin delivery are efficient in maintaining glycaemic control: an initial comparison with subcutaneous administration. Pharm Res 24: 1381-8.
Ogundele M and Okafor HK (2017). Transdermal Drug Delivery: Microneedles, Their Fabrication and Current Trends in Delivery Methods. Int J Pharm Res 18: 1-14.
Olatunji O, Das DB, Garland MJ, Belaid L and Donnelly RF (2013). Influence of array interspacing on the force required for successful microneedle skin penetration: Theoretical and practical approaches. J. Pharm. Sci 102: 1209-1221.
Parhi R, Suresh P and Patnaik S (2015). Physical Means of Stratum Corneum Barrier Manipulation to Enhance Transdermal Drug Delivery. Current Drug Delivery 12: 122-138
Park JH, Allen MG and Prausnitz MR (2005). Biodegradable polymer microneedles Fabrication, mechanics and transdermal drug delivery. Journal of Controlled Release 104: 51-66.
Park JH, Allen MG and Prausnitz MR (2006). Polymer microneedles for controlled-release drug delivery. Pharm. Res 23: 1008-19.
Paudel KS, Milewski M, Swadley CL, Brogden NK, Ghosh P and Stinchcomb AL (2010). Challenges and opportunities in dermal/ transdermal delivery. Ther. Deliv 1: 109-131.
Paul OM, Gaspar J and Ruther P (2007). Advanced Silicon Microstructures, Sensors, and Systems. IEEJ Trans 2: 199-215.
Pearton M, Kang SM, Song JM, Kim YC, Quan FS, Anstey A, Ivory M, Prausnitz MR, Compans RW and Birchall JC (2010). Influenza virus-like particles coated onto microneedles can elicit stimulatory effects on Langerhans cells in human skin. Vaccine 28: 6104-6113.
Perennes F, Marmiroli B, Matteucci M, Tormen M, Vaccari L and DiFabrizio E (2006). Sharp beveled tip hollow microneedle arrays fabricated by LIGA and 3D soft lithography with polyvinyl alcohol. J.Micromech.Microeng 16: 473-479.
Prausnitz MR , Mikszta JA, Cormier M and Andrianov AK (2009). Microneedle-based vaccines. Curr. Top. Microbiol. Immunol 333: 369-393.
Prausnitz MR and Langer R (2008). Transdermal drug delivery. Nat. Biotechnol 26: 1261-1268.
Prausnitz MR (2004). Microneedles for transdermal drug delivery. Adv Drug Deliv Rev 56: 581-587.
Purohit AG (2014). Formulation and evaluation of coated microneedles for the treatment of hairloss. Int J Res Rev Pharm Appl Sci 4: 1083-1101.
Rejinold NS, Shin JH, Seok HY and Kim YC(2015). Biomedical applications of microneedles in therapeutics: Recent advancements and implications in drug delivery. Expert Opinion on Drug Delivery 13: 109-131.
Ripolin A, Quinn J, Larrañeta E, Vicente-Perez EM, Barry J and Donnelly RF (2017). Successful application of large microneedle patches by human Volunteers. International Journal of Pharmaceutics 521: 92-101.
Roby KD and DiNardo A (2013). Innate immunity and the role of the antimicrobial peptide cathelicidin in inflammatory skin disease.Drug Discov. Today: Dis. Mech 10: 79-82.
Roxhed N, Griss P and Stemme G (2008). Membrane-sealed hollow microneedles and related administration schemes for transdermal drug delivery. Biomed. Microdev 10: 271-279.
Runyan WR and Bean KE (1990). Semiconductor Integrated Circuit Processing Technology, 1st ed. Massachusetss, Addison-Wesley.
Sammoura F, Kang JJ, Heo YM, Jung JS and Lin LW (2007). Polymeric microneedle fabrication using a microinjection molding technique. Microsyst.Technol 13: 517-522.
Schoellhammer CM, Blankschtein D and Langer R (2014). Skin permeabilization for transdermal drug delivery: recent advances and future prospects. Expert Opin. Drug Deliv 11: 393-407.
Sharma D(2018).Microneedles: an approach in transdermal drug delivery: a Review. PharmaTutor 6: 7-15.
Singh TRR, Mcmillan H, Mooney K, Alkilani AZ and Donnelly RF (2013). Microfluidic Devices for Biomedical Applications. Biomaterials 6: 185-230.
Sivamani RK, Liepmann D and Maibach HI(2007).Microneedles and transdermal applications. Expert Opinion on Drug Delivery 4: 19-25.
Sivaraman A and Banga AK (2017). Novel in situ forming hydrogel microneedles for transdermal drug delivery. Drug Deliv. and Transl. Res 7: 16-26.
Sokolowski CJ, Giovannitti JA and Boynes SG (2010). Needle phobia: etiology, adverse consequences, and patient management. Dent. Clin. North Am 54: 731.
Sua´rez-Varela MTM (2009). Study on the use of a smart pillbox to improve treatment compliance. Aten. Primaria 41: 185.
Subedi RK, Oh SY, Chun MK and Choi HK(2010). Recent advances in transdermal drug delivery. Arch. Pharm. Res 33: 339-351.
Sullivan SP, Murthy N and Prausnitz MR (2008). Minimally invasive protein delivery with rapidly dissolving polymer microneedles. Adv. Mater 20: 933-8.
Tarbox TN , Watts AB, Cui Z and Williams RO (2017). An update on coating/manufacturing techniques of microneedles. Drug Deliv. Transl. Res 8: 1-16.
Tuan-Mahmood TM, McCrudden MT, Torrisi BM, McAlister E, Garland MJ, Singh TRR and Donnelly RF (2013). Microneedles for intradermal and transdermal drug delivery. Eur. J. Pharm. Sci 50: 623-637.
Verbaan FJ, Bal SM, Van den Berg DJ, Dijksman JA, van Hecke M, Verpoorten H, Van den Berg A, Luttge R and Bouwstra JA(2008). Improved piercing of microneedle arrays in dermatomed human skin by an impact insertion method. J. Control. Release 128: 80-88.
Verbaan FJ, Bal SM, van den Berg DJ, Groenink WH, verpoorten H, Luttge R and Bouwstra JA (2007). Assembled microneedle arrays enhance the transport of compounds varying over a large range of molecular weight across human dermatomed skin. J.Control.Release 117: 238-245.
Verhoeven M, Bystrova S, Winnubst L, Qureshi H, de Gruijl TD, Scheper RJ and Luttge R (2012). Applying ceramic nanoporous microneedle arrays as a transport interface in egg plants and an ex-vivo human skin model. Microelectron.Eng 98: 659-662.
Vicente-Perez EM, Larrañeta E, McCrudden MTC, Kissenpfennig A, Hegarty S, McCarthy HO and Donnelly RF(2017). Repeat application of microneedles does not alter skin appearance or barrier function and causes no measurable disturbance of serum
biomarkers of infection, inflammation or immunity in mice in vivo. European Journal of Pharmaceutics and Biopharmaceutics 117: 400-407.
Vinayakumar KB, Hegde GM, Nayak MM, Dinesh NS and Rajanna K(2014). Fabrication and characterization of gold coated hollow silicon microneedle array for drug delivery. Microelectron. Eng 128: 12-18.
Vora LK, Vavia PR, Larrañeta E, Bell SEJ and Donnelly RF (2018). Novel nanosuspension-based dissolving microneedle arrays for transdermal delivery of a hydrophobic drug. Journal of Interdisciplinary Nanomedicine 3: 89-101.
Wang PC , Paik SJ , Kim J ,Kim SH and Allen MG (2011). Hypodermic-needle-like hollow polymer microneedle array using UV lithography into micromolds. Micro Electro Mechanical Systems 24: 23-27.
Wang PM, Cornwell M, Hill J and Prausnitz MR (2006). Precise Microinjection into Skin Using Hollow Microneedles. J. Invest. Dermatol 126: 1080-1087.
Wermeling DP, Banks SL, Hudson DA, Gill HS, Gupta J, Prausnitz MR and Stinchcomb AL (2008). Microneedles permit transdermal delivery of a skin-impermeant medication to humans. Proc Natl Acad Sci USA 105: 2058-63.
Widera G, Johnson J, Kim L, Libiran L, Nyam K, Daddona PE and Cormier M(2006). Effect of delivery parameters on immunization to ovalbumin following intracutaneous administration by a coated microneedle array patch system. Vaccine 24: 1653-1664.
Wijaya M, Moore JS, Kashlan O, Kamath R, Wang PM, O’Neal JM and Prausnitz MR (2006). Microinfusion Using Hollow Microneedles. Pharmaceutical Research 23: 104-113.
Wong TW (2014). Electrical, magnetic, photomechanical and cavitational waves to overcome skin barrier for transdermal drug delivery. J. Control. Release 193: 257-269.
Yadav JDDN (2011). Microneedles:Promising technique for transdermal drug delivery. International Journal of Pharma and Bio Sciences 2: 684-708.
Yan G, Warner KS, Zhang J, Sharma S and Gale BK (2010). Evaluation needle length and density of microneedle arrays in the pretreatment of skin for transdermal drug delivery. Int J Pharm 391: 7-12.