The Microneedle Drug Delivery System and some Recent Obstacles in its
Implementation

Bhagyesh      Dugad; Sankha      Bhattacharya
doi:10.2174/2210681213666230516155253
Abstract

Transdermal Drug Delivery (TDD) is a non-painful way of systemically delivering medications by applying a drug formulation to intact, healthy skin. The drug particles’ limitations, including the molecular weight and hydrophilicity, preclude TDD from being exploited extensively. Microneedle arrays (MNA) are an efficient way for medication delivery via the skin. Microneedles enhance medication administration. Microneedles are either long, hollow, or coated. They are designed to target the skin as quickly and safely as possible, without the use of chemical, nanoparticle, or hypodermic injections and without requiring micro-pen or physical strategies. Solid microneedles include micropores, whereas hollow microneedles provide a more profound passage into the dermis. Investigations have been conducted on the use of dissolving microneedles for the delivery of vaccines, while coated microneedles have been utilized to efficiently deliver vaccines. This paper attempts to provide a comprehensive summary of the current state of MNA science, with a focus on methodologies, issues, implementations, and the types of materials lately dispersed by such devices. In addition, some information regarding the components and manufacturing methods is provided. Metals, silicone, ceramics, synthetic materials, and biodegradable polymers, such as carbohydrates, can be utilized to manufacture microneedles.
Graphical Abstract

[1]
Kang, N.W.; Kim, S.; Lee, J.Y.; Kim, K.T.; Choi, Y.; Oh, Y.; Kim, J.; Kim, D.D.; Park, J.H. Microneedles for drug delivery: Recent advances in materials and geometry for preclinical and clinical studies. Expert Opin. Drug Deliv.,  2021, 18(7), 929-947.
 [http://dx.doi.org/10.1080/17425247.2021.1828860] [PMID: 32975144]

[2]
Queiroz, M.L.B.; Shanmugam, S.; Santos, L.N.S.; Campos, C.A.; Santos, A.M.; Batista, M.S.; Araújo, A.A.S.; Serafini, M.R. Microneedles as an alternative technology for transdermal drug delivery systems: A patent review. Expert Opin. Ther. Pat.,  2020, 30(6), 433-452.
 [http://dx.doi.org/10.1080/13543776.2020.1742324] [PMID: 32164470]

[3]
Manoj, H; Gupta, P; Mohan, L; Nagai, M; Wankhar, S; Santra, TS Microneedles: Current trends and applications.  Microfluidics and Bio-MEMS,  ((1st ed.). ) 2020, 275-342.

[4]
Aung, N.N.; Ngawhirunpat, T.; Rojanarata, T.; Patrojanasophon, P.; Pamornpathomkul, B.; Opanasopit, P. Fabrication, characterization and comparison of α-arbutin loaded dissolving and hydrogel forming microneedles. Int. J. Pharm.,  2020, 586, 119508.
 [http://dx.doi.org/10.1016/j.ijpharm.2020.119508] [PMID: 32512227]

[5]
Wang, R.; Jiang, G.; Aharodnikau, U.E.; Yunusov, K.; Sun, Y.; Liu, T.; Solomevich, S.O. Recent advances in polymer microneedles for drug transdermal delivery: Design strategies and applications. Macromol. Rapid Commun.,  2022, 43(8), 2200037.
 [http://dx.doi.org/10.1002/marc.202200037] [PMID: 35286762]

[6]
Amani, H.; Shahbazi, M.A.; D’Amico, C.; Fontana, F.; Abbaszadeh, S.; Santos, H.A. Microneedles for painless transdermal immunotherapeutic applications. J. Control. Release,  2021, 330, 185-217.
 [http://dx.doi.org/10.1016/j.jconrel.2020.12.019] [PMID: 33340568]

[7]
Caffarel-Salvador, E.; Kim, S.; Soares, V.; Tian, R.Y.; Stern, S.R.; Minahan, D.; Yona, R.; Lu, X.; Zakaria, F.R.; Collins, J.; Wainer, J.; Wong, J.; McManus, R.; Tamang, S.; McDonnell, S.; Ishida, K.; Hayward, A.; Liu, X.; Hubálek, F.; Fels, J.; Vegge, A.; Frederiksen, M.R.; Rahbek, U.; Yoshitake, T.; Fujimoto, J.; Roxhed, N.; Langer, R.; Traverso, G. A microneedle platform for buccal macromolecule delivery. Sci. Adv.,  2021, 7(4), eabe2620.
 [http://dx.doi.org/10.1126/sciadv.abe2620] [PMID: 33523951]

[8]
Larrañeta, E.; Lutton, R.E.M.; Woolfson, A.D.; Donnelly, R.F. Microneedle arrays as transdermal and intradermal drug delivery systems: Materials science, manufacture and commercial development. Mater. Sci. Eng. Rep.,  2016, 104, 1-32.
 [http://dx.doi.org/10.1016/j.mser.2016.03.001]

[9]
Wei, F.; Wang, Q.; Liu, H.; Yang, X.; Cao, W.; Zhao, W.; Li, Y.; Zheng, L.; Ma, T.; Wang, Q. High efficacy combined microneedles array with methotrexate nanocrystals for effective anti-rheumatoid arthritis. Int. J. Nanomedicine,  2022, 17, 2397-2412.
 [http://dx.doi.org/10.2147/IJN.S365523] [PMID: 35637840]

[10]
Haghniaz, R.; Kim, H.J.; Montazerian, H.; Baidya, A.; Tavafoghi, M.; Chen, Y.; Zhu, Y.; Karamikamkar, S.; Sheikhi, A.; Khademhosseini, A. Tissue adhesive hemostatic microneedle arrays for rapid hemorrhage treatment. Bioact. Mater.,  2023, 23, 314-327.
 [http://dx.doi.org/10.1016/j.bioactmat.2022.08.017] [PMID: 36439081]

[11]
Tijani, A.; Dogra, P.; Peláez, M.J.; Wang, Z.; Cristini, V.; Puri, A. Mechanistic modeling-guided optimization of microneedle-based skin patch for rapid transdermal delivery of naloxone for opioid overdose treatment. Drug Deliv. Transl. Res.,  2023, 13(1), 320-338.
 [http://dx.doi.org/10.1007/s13346-022-01202-w] [PMID: 35879533]

[12]
Men, Z.; Su, T.; Tang, Z.; Liang, J.; Shen, T. Tacrolimus nanocrystals microneedle patch for plaque psoriasis. Int. J. Pharm.,  2022, 627, 122207.
 [http://dx.doi.org/10.1016/j.ijpharm.2022.122207] [PMID: 36122614]

[13]
Economidou, S.N.; Pere, C.P.P.; Reid, A.; Uddin, M.J.; Windmill, J.F.C.; Lamprou, D.A.; Douroumis, D. 3D printed microneedle patches using stereolithography (SLA) for intradermal insulin delivery. Mater. Sci. Eng. C,  2019, 102, 743-755.
 [http://dx.doi.org/10.1016/j.msec.2019.04.063] [PMID: 31147046]

[14]
Johnson, AR; Procopio, AT Low cost additive manufacturing of microneedle masters. 3D Print. Med.,  2019, 5(1), 1-0.
 [http://dx.doi.org/10.1186/s41205-019-0039-x]

[15]
Girija Sravani, K; Desala, RK; Chand, P; Sathvik, K; Srinivasa Rao, K; Lay-Ekuakille, A Design and analysis of bio-inspired micro-needle for drug delivery applications. IEEE Trans Nanobioscience,  2023, 22(2), 237-244.
 [http://dx.doi.org/10.1109/TNB.2022.3185633] [PMID: 35737616]

[16]
Fang, J.H.; Liu, C.H.; Hsu, R.S.; Chen, Y.Y.; Chiang, W.H.; Wang, H.M.D.; Hu, S.H. Transdermal composite microneedle composed of mesoporous iron oxide nanoraspberry and PVA for androgenetic alopecia treatment. Polymers,  2020, 12(6), 1392.
 [http://dx.doi.org/10.3390/polym12061392] [PMID: 32580298]

[17]
Chang, H.; Zheng, M.; Chew, S.W.T.; Xu, C. Advances in the formulations of microneedles for manifold biomedical applications. Adv. Mater. Technol.,  2020, 5(4), 1900552.
 [http://dx.doi.org/10.1002/admt.201900552]

[18]
Liu, T.; Luo, G.; Xing, M. Biomedical applications of polymeric microneedles for transdermal therapeutic delivery and diagnosis: current status and future perspectives. Adv. Ther.,  2020, 3(9), 1900140.
 [http://dx.doi.org/10.1002/adtp.201900140]

[19]
Zhang, X; Chen, G; Yu, Y; Sun, L; Zhao, Y Bioinspired adhesive and antibacterial microneedles for versatile transdermal drug delivery. Research,  2020, 2020, 3672120.
 [http://dx.doi.org/10.34133/2020/3672120]

[20]
Peña-Juárez, M.C.; Guadarrama-Escobar, O.R.; Escobar-Chávez, J.J. Transdermal delivery systems for biomolecules. J. Pharm. Innov.,  2022, 17(2), 319-332.
 [http://dx.doi.org/10.1007/s12247-020-09525-2] [PMID: 33425065]

[21]
Tripathy, N.; Wang, J.; Tung, M.; Conway, C.; Chung, E.J. Transdermal delivery of kidney-targeting nanoparticles using dissolvable microneedles. Cell. Mol. Bioeng.,  2020, 13(5), 475-486.
 [http://dx.doi.org/10.1007/s12195-020-00622-3] [PMID: 33184578]

[22]
Bilal, M.; Mehmood, S.; Raza, A.; Hayat, U.; Rasheed, T.; Iqbal, H.M.N. Microneedles in smart drug delivery. Adv. Wound Care,  2021, 10(4), 204-219.
 [http://dx.doi.org/10.1089/wound.2019.1122] [PMID: 32320365]

[23]
Hutton, A.R.J.; Ubah, O.; Barelle, C.; Donnelly, R.F. Enhancing the transdermal delivery of ‘next generation’ variable new antigen receptors using microarray patch technology: A proof-of-concept study. J. Pharm. Sci.,  2022, 111(12), 3362-3376.
 [http://dx.doi.org/10.1016/j.xphs.2022.08.027] [PMID: 36037879]

[24]
Mansoor, I.; Eassa, H.A.; Mohammed, K.H.A.; Abd El-Fattah, M.A.; Abdo, M.H.; Rashad, E.; Eassa, H.A.; Saleh, A.; Amin, O.M.; Nounou, M.I.; Ghoneim, O. Microneedle-based vaccine delivery: review of an emerging technology. AAPS PharmSciTech,  2022, 23(4), 103.
 [http://dx.doi.org/10.1208/s12249-022-02250-8] [PMID: 35381906]

[25]
Nguyen, T.T.; Oh, Y.; Kim, Y.; Shin, Y.; Baek, S.K.; Park, J.H. Progress in microneedle array patch (MAP) for vaccine delivery. Hum. Vaccin. Immunother.,  2021, 17(1), 316-327.
 [http://dx.doi.org/10.1080/21645515.2020.1767997] [PMID: 32667239]

[26]
O’Shea, J.; Prausnitz, M.R.; Rouphael, N. Dissolvable microneedle patches to enable increased access to vaccines against SARS-CoV-2 and future pandemic outbreaks. Vaccines,  2021, 9(4), 320.
 [http://dx.doi.org/10.3390/vaccines9040320] [PMID: 33915696]

[27]
Sebastian, R.; Guillerm, T.; Tjulkins, F.; Hu, Y.; Clover, A.J.P.; Lyness, A.; O’Mahony, C. A comparison of flow- and pressure-controlled infusion strategies for microneedle-based transdermal drug delivery. Annu. Int. Conf. IEEE Eng. Med. Biol. Soc.,  2022, 2022, 2573-2576.
 [http://dx.doi.org/10.1109/EMBC48229.2022.9871582] [PMID: 36085690]

[28]
Gupta, J.; Gupta, R.; Vanshita Microneedle technology: An insight into recent advancements and future trends in drug and vaccine delivery. Assay Drug Dev. Technol.,  2021, 19(2), 97-114.
 [http://dx.doi.org/10.1089/adt.2020.1022] [PMID: 33297823]

[29]
Du, G.; He, P.; Zhao, J.; He, C.; Jiang, M.; Zhang, Z.; Zhang, Z.; Sun, X. Polymeric microneedle-mediated transdermal delivery of melittin for rheumatoid arthritis treatment. J. Control. Release,  2021, 336, 537-548.
 [http://dx.doi.org/10.1016/j.jconrel.2021.07.005] [PMID: 34237400]

[30]
Menon, I.; Bagwe, P.; Gomes, K.B.; Bajaj, L.; Gala, R.; Uddin, M.N.; D’Souza, M.J.; Zughaier, S.M. Microneedles: A new generation vaccine delivery system. Micromachines,  2021, 12(4), 435.
 [http://dx.doi.org/10.3390/mi12040435] [PMID: 33919925]

[31]
Yoneda, S.; Torisu, T.; Uchiyama, S. Development of syringes and vials for delivery of biologics: Current challenges and innovative solutions. Expert Opin. Drug Deliv.,  2021, 18(4), 459-470.
 [http://dx.doi.org/10.1080/17425247.2021.1853699] [PMID: 33217252]

[32]
Sabri, A.H.; Kim, Y.; Marlow, M.; Scurr, D.J.; Segal, J.; Banga, A.K.; Kagan, L.; Lee, J.B. Intradermal and transdermal drug delivery using microneedles – Fabrication, performance evaluation and application to lymphatic delivery. Adv. Drug Deliv. Rev.,  2020, 153, 195-215.
 [http://dx.doi.org/10.1016/j.addr.2019.10.004] [PMID: 31634516]

[33]
Kathuria, H.; Kang, K.; Cai, J.; Kang, L. Rapid microneedle fabrication by heating and photolithography. Int. J. Pharm.,  2020, 575, 118992.
 [http://dx.doi.org/10.1016/j.ijpharm.2019.118992] [PMID: 31884060]

[34]
Wu, M.; Zhang, Y.; Huang, H.; Li, J.; Liu, H.; Guo, Z.; Xue, L.; Liu, S.; Lei, Y. Assisted 3D printing of microneedle patches for minimally invasive glucose control in diabetes. Mater. Sci. Eng. C,  2020, 117, 111299.
 [http://dx.doi.org/10.1016/j.msec.2020.111299] [PMID: 32919660]

[35]
Bolton, C.J.W.; Howells, O.; Blayney, G.J.; Eng, P.F.; Birchall, J.C.; Gualeni, B.; Roberts, K.; Ashraf, H.; Guy, O.J. Hollow silicon microneedle fabrication using advanced plasma etch technologies for applications in transdermal drug delivery. Lab Chip,  2020, 20(15), 2788-2795.
 [http://dx.doi.org/10.1039/D0LC00567C] [PMID: 32632424]

[36]
Ye, R.; Yang, J.; Li, Y.; Zheng, Y.; Yang, J.; Li, Y.; Liu, B.; Jiang, L. Fabrication of tip-hollow and tip-dissolvable microneedle arrays for transdermal drug delivery. ACS Biomater. Sci. Eng.,  2020, 6(4), 2487-2494.
 [http://dx.doi.org/10.1021/acsbiomaterials.0c00120] [PMID: 33455301]

[37]
Chi, J.; Zhang, X.; Chen, C.; Shao, C.; Zhao, Y.; Wang, Y. Antibacterial and angiogenic chitosan microneedle array patch for promoting wound healing. Bioact. Mater.,  2020, 5(2), 253-259.
 [http://dx.doi.org/10.1016/j.bioactmat.2020.02.004] [PMID: 32128464]

[38]
Ahmad, Z.; Khan, M.I.; Siddique, M.I.; Sarwar, H.S.; Shahnaz, G.; Hussain, S.Z.; Bukhari, N.I.; Hussain, I.; Sohail, M.F. Fabrication and characterization of thiolated chitosan microneedle patch for transdermal delivery of tacrolimus. AAPS PharmSciTech,  2020, 21(2), 68.
 [http://dx.doi.org/10.1208/s12249-019-1611-9] [PMID: 31950394]

[39]
Kim, S.; Yang, H.; Eum, J.; Ma, Y.; Fakhraei Lahiji, S.; Jung, H. Implantable powder-carrying microneedles for transdermal delivery of high-dose insulin with enhanced activity. Biomaterials,  2020, 232, 119733.
 [http://dx.doi.org/10.1016/j.biomaterials.2019.119733] [PMID: 31901501]

[40]
Krieger, K.J.; Bertollo, N.; Dangol, M.; Sheridan, J.T.; Lowery, M.M.; O’Cearbhaill, E.D. Simple and customizable method for fabrication of high-aspect ratio microneedle molds using low-cost 3D printing. Microsyst. Nanoeng.,  2019, 5(1), 42.
 [http://dx.doi.org/10.1038/s41378-019-0088-8] [PMID: 31645996]

[41]
Kusama, S.; Sato, K.; Matsui, Y.; Kimura, N.; Abe, H.; Yoshida, S.; Nishizawa, M. Transdermal electroosmotic flow generated by a porous microneedle array patch. Nat. Commun.,  2021, 12(1), 658.
 [http://dx.doi.org/10.1038/s41467-021-20948-4] [PMID: 33510169]

[42]
Dardano, P.; De Martino, S.; Battisti, M.; Miranda, B.; Rea, I.; De Stefano, L. One-shot fabrication of polymeric hollow microneedles by standard photolithography. Polymers,  2021, 13(4), 520.
 [http://dx.doi.org/10.3390/polym13040520] [PMID: 33572383]

[43]
McCrudden, M.T.C.; Alkilani, A.Z.; McCrudden, C.M.; McAlister, E.; McCarthy, H.O.; Woolfson, A.D.; Donnelly, R.F. Design and physicochemical characterisation of novel dissolving polymeric microneedle arrays for transdermal delivery of high dose, low molecular weight drugs. J. Control. Release,  2014, 180(100), 71-80.
 [http://dx.doi.org/10.1016/j.jconrel.2014.02.007] [PMID: 24556420]

[44]
Shang, H.; Younas, A.; Zhang, N. Recent advances on transdermal delivery systems for the treatment of arthritic injuries: from classical treatment to nanomedicines. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol.,  2022, 14(3), e1778.
 [http://dx.doi.org/10.1002/wnan.1778] [PMID: 35112483]

[45]
Shah, V.; Choudhury, B.K. Fabrication, physicochemical characterization, and performance evaluation of biodegradable polymeric microneedle patch system for enhanced transcutaneous flux of high molecular weight therapeutics. AAPS PharmSciTech,  2017, 18(8), 2936-2948.
 [http://dx.doi.org/10.1208/s12249-017-0774-5] [PMID: 28432615]

[46]
Kearney, M.C.; Caffarel-Salvador, E.; Fallows, S.J.; McCarthy, H.O.; Donnelly, R.F. Microneedle-mediated delivery of donepezil: Potential for improved treatment options in Alzheimer’s disease. Eur. J. Pharm. Biopharm.,  2016, 103, 43-50.
 [http://dx.doi.org/10.1016/j.ejpb.2016.03.026] [PMID: 27018330]

[47]
a) Guillot, AJ; Merino-Gutiérrez, P; Bocchino, A; O'Mahony, C; Giner, RM; Recio, MC; Garrigues, TM; Melero, A Exploration of microneedle-assisted skin delivery of cyanocobalamin formulated in ultraflexible lipid vesicles. Eur J Pharm Biopharm,  2022, 177, 184-198.
 [http://dx.doi.org/10.1016/j.ejpb.2022.06.015] [PMID: 35787430]; 
b) Alkilani, A.Z.; McCrudden, MT Donnelly, RF Transdermal drug delivery: Innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum. Pharmaceutics,  2022, 7(4), 438-470.
 [http://dx.doi.org/10.1016/j.ejpb.2022.06.015]

[48]
Kirkby, M.; Hutton, A.R.J.; Donnelly, R.F. Microneedle mediated transdermal delivery of protein, peptide and antibody based therapeutics: current status and future considerations. Pharm. Res.,  2020, 37(6), 117.
 [http://dx.doi.org/10.1007/s11095-020-02844-6] [PMID: 32488611]

[49]
Waghule, T.; Singhvi, G.; Dubey, S.K.; Pandey, M.M.; Gupta, G.; Singh, M.; Dua, K. Microneedles: A smart approach and increasing potential for transdermal drug delivery system. Biomed. Pharmacother.,  2019, 109, 1249-1258.
 [http://dx.doi.org/10.1016/j.biopha.2018.10.078] [PMID: 30551375]

[50]
Ita, K. Transdermal delivery of drugs with microneedles—potential and challenges. Pharmaceutics,  2015, 7(3), 90-105.
 [http://dx.doi.org/10.3390/pharmaceutics7030090] [PMID: 26131647]

[51]
Vora, L.K.; Courtenay, A.J.; Tekko, I.A.; Larrañeta, E.; Donnelly, R.F. Pullulan-based dissolving microneedle arrays for enhanced transdermal delivery of small and large biomolecules. Int. J. Biol. Macromol.,  2020, 146, 290-298.
 [http://dx.doi.org/10.1016/j.ijbiomac.2019.12.184] [PMID: 31883883]

[52]
Vora, L.K.; Vavia, P.R.; Larrañeta, E.; Bell, S.E.J.; Donnelly, R.F. Novel nanosuspension-based dissolving microneedle arrays for transdermal delivery of a hydrophobic drug. J. Interdiscip. Nanomed.,  2018, 3(2), 89-101.
 [http://dx.doi.org/10.1002/jin2.41] [PMID: 30069310]

[53]
Sharma, S.; Hatware, K.; Bhadane, P.; Sindhikar, S.; Mishra, D.K. Recent advances in microneedle composites for biomedical applications: Advanced drug delivery technologies. Mater. Sci. Eng. C,  2019, 103, 109717.
 [http://dx.doi.org/10.1016/j.msec.2019.05.002] [PMID: 31349403]

[54]
Rodgers, A.M.; Cordeiro, A.S.; Kissenpfennig, A.; Donnelly, R.F. Microneedle arrays for vaccine delivery: The possibilities, challenges and use of nanoparticles as a combinatorial approach for enhanced vaccine immunogenicity. Expert Opin. Drug Deliv.,  2018, 15(9), 851-867.
 [http://dx.doi.org/10.1080/17425247.2018.1505860] [PMID: 30051726]

[55]
Cho Lee, A-R. Microneedle-mediated delivery of cosmeceutically relevant nucleoside and peptides in human skin: challenges and strategies for dermal delivery. J. Pharm. Investig.,  2019, 49(6), 587-601.
 [http://dx.doi.org/10.1007/s40005-019-00438-y]

[56]
Liu, G.S.; Kong, Y.; Wang, Y.; Luo, Y.; Fan, X.; Xie, X.; Yang, B.R.; Wu, M.X. Microneedles for transdermal diagnostics: Recent advances and new horizons. Biomaterials,  2020, 232, 119740.
 [http://dx.doi.org/10.1016/j.biomaterials.2019.119740] [PMID: 31918227]

[57]
Huang, D.; Li, J.; Li, T.; Wang, Z.; Wang, Q.; Li, Z. Recent advances on fabrication of microneedles on the flexible substrate. J. Micromech. Microeng.,  2021, 31(7), 073001.
 [http://dx.doi.org/10.1088/1361-6439/ac0513]

[58]
Thakur, R.R.S.; Tekko, I.A.; Al-Shammari, F.; Ali, A.A.; McCarthy, H.; Donnelly, R.F. Rapidly dissolving polymeric microneedles for minimally invasive intraocular drug delivery. Drug Deliv. Transl. Res.,  2016, 6(6), 800-815.
 [http://dx.doi.org/10.1007/s13346-016-0332-9] [PMID: 27709355]

[59]
Shen, D.; Yu, H.; Wang, L.; Chen, X.; Feng, J.; Zhang, Q.; Xiong, W.; Pan, J.; Han, Y.; Liu, X. Biodegradable phenylboronic acid-modified ε-polylysine for glucose-responsive insulin delivery via transdermal microneedles. J. Mater. Chem. B Mater. Biol. Med.,  2021, 9(30), 6017-6028.
 [http://dx.doi.org/10.1039/D1TB00880C] [PMID: 34259305]

[60]
Xie, L.; Zeng, H.; Sun, J.; Qian, W. Engineering microneedles for therapy and diagnosis: A survey. Micromachines (Basel),  2020, 11(3), 271.
 [http://dx.doi.org/10.3390/mi11030271] [PMID: 32150866]

[61]
Lanza, J.S.; Pomel, S.; Loiseau, P.M.; Frézard, F. Recent advances in amphotericin B delivery strategies for the treatment of leishmaniases. Expert Opin. Drug Deliv.,  2019, 16(10), 1063-1079.
 [http://dx.doi.org/10.1080/17425247.2019.1659243] [PMID: 31433678]

[62]
Qindeel, M.; Ullah, M.H.; Fakhar-ud-Din; Ahmed, N.; Rehman, A. Recent trends, challenges and future outlook of transdermal drug delivery systems for rheumatoid arthritis therapy. J. Control. Release,  2020, 327, 595-615.
 [http://dx.doi.org/10.1016/j.jconrel.2020.09.016] [PMID: 32920080]

[63]
Tarbox, T.N.; Watts, A.B.; Cui, Z.; Williams, R.O., III An update on coating/manufacturing techniques of microneedles. Drug Deliv. Transl. Res.,  2018, 8(6), 1828-1843.
 [http://dx.doi.org/10.1007/s13346-017-0466-4] [PMID: 29288358]

[64]
Yao, W.; Li, D.; Zhao, Y.; Zhan, Z.; Jin, G.; Liang, H.; Yang, R. 3D printed multi-functional hydrogel microneedles based on high-precision digital light processing. Micromachines,  2019, 11(1), 17.
 [http://dx.doi.org/10.3390/mi11010017] [PMID: 31877987]

[65]
Sachdeva, V.; Banga, A.K. Microneedles and their applications. Recent Pat. Drug Deliv. Formul.,  2011, 5(2), 95-132.
 [http://dx.doi.org/10.2174/187221111795471445] [PMID: 21453248]

[66]
Yang, J.; Zhang, H.; Hu, T.; Xu, C.; Jiang, L.; Shrike Zhang, Y.; Xie, M. Recent advances of microneedles used towards stimuli-responsive drug delivery, disease theranostics, and bioinspired applications. Chem. Eng. J.,  2021, 426, 130561.
 [http://dx.doi.org/10.1016/j.cej.2021.130561]

[67]
Azmana, M.; Mahmood, S.; Hilles, A.R.; Mandal, U.K.; Saeed Al-Japairai, K.A.; Raman, S. Transdermal drug delivery system through polymeric microneedle: A recent update. J. Drug Deliv. Sci. Technol.,  2020, 60, 101877.
 [http://dx.doi.org/10.1016/j.jddst.2020.101877]

[68]
Seetharam, A.A.; Choudhry, H.; Bakhrebah, M.A.; Abdulaal, W.H.; Gupta, M.S.; Rizvi, S.M.D.; Alam, Q.; Siddaramaiah; Gowda, D.V.; Moin, A. Microneedles drug delivery systems for treatment of cancer: A recent update. Pharmaceutics,  2020, 12(11), 1101.
 [http://dx.doi.org/10.3390/pharmaceutics12111101] [PMID: 33212921]

[69]
Yang, Q.; Zhong, W.; Xu, L.; Li, H.; Yan, Q.; She, Y.; Yang, G. Recent progress of 3D-printed microneedles for transdermal drug delivery. Int. J. Pharm.,  2021, 593, 120106.
 [http://dx.doi.org/10.1016/j.ijpharm.2020.120106] [PMID: 33232756]

[70]
Dervisevic, M.; Dervisevic, E.; Esser, L.; Easton, C.D.; Cadarso, V.J.; Voelcker, N.H. Wearable microneedle array-based sensor for transdermal monitoring of pH levels in interstitial fluid. Biosens. Bioelectron.,  2023, 222, 114955. Epub ahead of print
 [http://dx.doi.org/10.1016/j.bios.2022.114955] [PMID: 36462430]

[71]
Alimardani, V.; Abolmaali, S.S.; Tamaddon, A.M.; Ashfaq, M. Recent advances on microneedle arrays-mediated technology in cancer diagnosis and therapy. Drug Deliv. Transl. Res.,  2021, 11(3), 788-816.
 [http://dx.doi.org/10.1007/s13346-020-00819-z] [PMID: 32740799]

[72]
Ahmed Saeed AL-Japairai, K.; Mahmood, S.; Hamed Almurisi, S.; Reddy Venugopal, J.; Rebhi Hilles, A.; Azmana, M.; Raman, S. Current trends in polymer microneedle for transdermal drug delivery. Int. J. Pharm.,  2020, 587, 119673.
 [http://dx.doi.org/10.1016/j.ijpharm.2020.119673] [PMID: 32739388]

[73]
Zhao, Z.; Chen, Y.; Shi, Y. Microneedles: A potential strategy in transdermal delivery and application in the management of psoriasis. RSC Advances,  2020, 10(24), 14040-14049.
 [http://dx.doi.org/10.1039/D0RA00735H] [PMID: 35498446]

[74]
Halder, J.; Gupta, S.; Kumari, R.; Gupta, G.D.; Rai, V.K. Microneedle array: Applications, recent advances, and clinical pertinence in transdermal drug delivery. J. Pharm. Innov.,  2021, 16(3), 550-565.
 [PMID: 32837607]

[75]
Kinvig, H.; Cottura, N.; Lloyd, A.; Frivold, C.; Mistilis, J.; Jarrahian, C.; Siccardi, M. Evaluating islatravir administered via microneedle array patch for long-acting HIV pre-exposure prophylaxis using physiologically based pharmacokinetic modelling. Eur. J. Drug Metab. Pharmacokinet.,  2022, 47(6), 855-868.
 [http://dx.doi.org/10.1007/s13318-022-00793-6] [PMID: 36178586]

[76]
Shrivastava, S.; Trung, T.Q.; Lee, N.E. Recent progress, challenges, and prospects of fully integrated mobile and wearable point-of-care testing systems for self-testing. Chem. Soc. Rev.,  2020, 49(6), 1812-1866.
 [http://dx.doi.org/10.1039/C9CS00319C] [PMID: 32100760]

[77]
Chen, X.; Wang, L.; Yu, H.; Li, C.; Feng, J.; Haq, F.; Khan, A.; Khan, R.U. Preparation, properties and challenges of the microneedles-based insulin delivery system. J. Control. Release,  2018, 288, 173-188.
 [http://dx.doi.org/10.1016/j.jconrel.2018.08.042] [PMID: 30189223]

[78]
Shin, C.I.; Jeong, S.D.; Rejinold, N.S.; Kim, Y.C. Microneedles for vaccine delivery: challenges and future perspectives. Ther. Deliv.,  2017, 8(6), 447-460.
 [http://dx.doi.org/10.4155/tde-2017-0032] [PMID: 28530151]

[79]
Rodgers, A.M.; McCrudden, M.T.C.; Vincente-Perez, E.M.; Dubois, A.V.; Ingram, R.J.; Larrañeta, E.; Kissenpfennig, A.; Donnelly, R.F. Design and characterisation of a dissolving microneedle patch for intradermal vaccination with heat-inactivated bacteria: A proof of concept study. Int. J. Pharm.,  2018, 549(1-2), 87-95.
 [http://dx.doi.org/10.1016/j.ijpharm.2018.07.049] [PMID: 30048778]

[80]
Hossain, M.K.; Ahmed, T.; Bhusal, P.; Subedi, R.K.; Salahshoori, I.; Soltani, M.; Hassanzadeganroudsari, M. Microneedle systems for vaccine delivery: The story so far. Expert Rev. Vaccines,  2020, 19(12), 1153-1166.
 [http://dx.doi.org/10.1080/14760584.2020.1874928] [PMID: 33427523]

[81]
Rejinold, N.S.; Shin, J.H.; Seok, H.Y.; Kim, Y.C. Biomedical applications of microneedles in therapeutics: Recent advancements and implications in drug delivery. Expert Opin. Drug Deliv.,  2016, 13(1), 109-131.
 [http://dx.doi.org/10.1517/17425247.2016.1115835] [PMID: 26559052]

[82]
Nagarkar, R.; Singh, M.; Nguyen, H.X.; Jonnalagadda, S. A review of recent advances in microneedle technology for transdermal drug delivery. J. Drug Deliv. Sci. Technol.,  2020, 59, 101923.
 [http://dx.doi.org/10.1016/j.jddst.2020.101923]

[83]
Kang, D.; Ge, Q.; Natabou, M.A.; Xu, W.; Liu, X.; Xu, B.; Bao, X.; Kalia, Y.N.; Chen, Y. Bolus delivery of palonosetron through skin by tip-loaded dissolving microneedles with short-duration iontophoresis: A potential strategy to rapidly relieve emesis associated with chemotherapy. Int. J. Pharm.,  2022, 628, 122294.
 [http://dx.doi.org/10.1016/j.ijpharm.2022.122294] [PMID: 36252645]

[84]
Ingrole, R.S.J.; Azizoglu, E.; Dul, M.; Birchall, J.C.; Gill, H.S.; Prausnitz, M.R. Trends of microneedle technology in the scientific literature, patents, clinical trials and internet activity. Biomaterials,  2021, 267, 120491.
 [http://dx.doi.org/10.1016/j.biomaterials.2020.120491] [PMID: 33217629]

[85]
Zvezdin, V.; Kasatkina, T.; Kasatkin, I.; Gavrilova, M.; Kazakova, O. Microneedle patch based on dissolving, detachable microneedle technology for improved skin quality of the periorbital region. Part 2: Clinical Evaluation. Int. J. Cosmet. Sci.,  2020, 42(5), 429-435.
 [http://dx.doi.org/10.1111/ics.12636] [PMID: 32485024]

[86]
Altuntaş, E.; Tekko, I.A.; Vora, L.K.; Kumar, N.; Brodsky, R.; Chevallier, O.; McAlister, E.; Kurnia Anjani, Q.; McCarthy, H.O.; Donnelly, R.F. Nestorone nanosuspension-loaded dissolving microneedles array patch: A promising novel approach for “on-demand” hormonal female-controlled peritcoital contraception. Int. J. Pharm.,  2022, 614, 121422.
 [http://dx.doi.org/10.1016/j.ijpharm.2021.121422] [PMID: 34958899]

[87]
Nayak, S.; Suryawanshi, S.; Bhaskar, V. Microneedle technology for transdermal drug delivery: applications and combination with other enhancing techniques. J. Drug Deliv. Ther.,  2016, 6(5), 65-83.

[88]
Guillot, A.J.; Cordeiro, A.S.; Donnelly, R.F.; Montesinos, M.C.; Garrigues, T.M.; Melero, A. Microneedle-based delivery: An overview of current applications and trends. Pharmaceutics,  2020, 12(6), 569.
 [http://dx.doi.org/10.3390/pharmaceutics12060569] [PMID: 32575392]

[89]
McAlister, E.; Dutton, B.; Vora, L.K.; Zhao, L.; Ripolin, A.; Zahari, D.S.Z.B.P.H.; Quinn, H.L.; Tekko, I.A.; Courtenay, A.J.; Kelly, S.A.; Rodgers, A.M.; Steiner, L.; Levin, G.; Levy-Nissenbaum, E.; Shterman, N.; McCarthy, H.O.; Donnelly, R.F. Directly compressed tablets: A novel drug‐containing reservoir combined with hydrogel‐forming microneedle arrays for transdermal drug delivery. Adv. Healthc. Mater.,  2021, 10(3), 2001256.
 [http://dx.doi.org/10.1002/adhm.202001256] [PMID: 33314714]

[90]
Alimardani, V.; Abolmaali, S.S.; Yousefi, G.; Rahiminezhad, Z.; Abedi, M.; Tamaddon, A.; Ahadian, S. Microneedle arrays combined with nanomedicine approaches for transdermal delivery of therapeutics. J. Clin. Med.,  2021, 10(2), 181.
 [http://dx.doi.org/10.3390/jcm10020181] [PMID: 33419118]

[91]
Rojekar, S.; Vora, L.K.; Tekko, I.A.; Volpe-Zanutto, F.; McCarthy, H.O.; Vavia, P.R.; Donnelly, R.F. Etravirine-loaded dissolving microneedle arrays for long-acting delivery. Eur. J. Pharm. Biopharm.,  2021, 165, 41-51.
 [http://dx.doi.org/10.1016/j.ejpb.2021.04.024] [PMID: 33971273]
Rights & Permissions Print Cite
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/2210681213666230516155253	Print ISSN 2210-6812
Publisher Name Bentham Science Publisher	Online ISSN 2210-6820
Nanoscience & Nanotechnology-Asia

The Microneedle Drug Delivery System and some Recent Obstacles in its Implementation

Abstract Play Pause

Graphical Abstract

Related Journals

Related Books

Abstract
