Generic placeholder image

Nanoscience & Nanotechnology-Asia

Editor-in-Chief

ISSN (Print): 2210-6812
ISSN (Online): 2210-6820

Review Article

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

Author(s): Bhagyesh Dugad and Sankha Bhattacharya*

Volume 13, Issue 4, 2023

Published on: 13 June, 2023

Article ID: e160523216980 Pages: 19

DOI: 10.2174/2210681213666230516155253

Price: $65

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
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version435msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[08:18:15] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[08:18:16] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • warninglog[08:18:16] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[08:18:16] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (165ms)time
  • Application (270ms)time
  • 1 x Application (61.99%)
    270ms
    1 x Booting (38.01%)
    165ms
    14 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.blade.php#?blade
    • includes.article_referencearticle_reference.blade.php#?blade
    • export_citation_formexport_citation_form.blade.php#?blade
    • includes.article_bottom_bannerarticle_bottom_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • includes.journal_right_bannerjournal_right_banner.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    36 statements were executed, 4 of which were duplicates, 32 unique. Show only duplicated160ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('316440840','',1,1740471495,1740471495) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740471495
      1.31msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('316440840','/article/131838',1,1740471495,1740471495)
      670μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) limit 1
      17.47msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 316440840
      • 1: 316440840
      • 2: 316440840
      • 3: 316440840
      • 4: 316440840
      • 5: 316440840
      • 6: 316440840
      • 7: 316440840
      • 8: 316440840
      • 9: 316440840
      • 10: 316440840
      • 11: 316440840
      • 12: 316440840
      • 13: 316440840
      • 14: 316440840
      • 15: 316440840
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • SELECT at.type_name, p.copyright, p.publisher_location,m.month,y.year, a.publish_on, a.nid article_nid,a.article_id, a.pmid, a.issue_id, a.title, a.abstract,a.podcast,a.altmetric_score,a.altmetric_url,a.kudos_url, a.page_count, a.first_page, a.elocator, a.last_page, i.publication_date, a.file_name, a.file_path, a.doi, a.is_epub,a.epub_type, a.volume_id, a.is_uploaded, a.editor_choice, a.is_epub, j.image_file_name, a.article_no, a.art_type AS article_type, a.supplementary_filename,a.html_filename,a.prc_filename,a.epub_filename, a.graph_abs_lg_filename, a.graph_abs_sm_filename, a.oa_image_lg_filename, a.oa_image_sm_filename, j.journal_banner,a.animated_abstract,a.erratum_in,a.erratum_for, (CASE WHEN a.issue_id =0 THEN j.epub_price ELSE j.price END) AS sell_price, j.epub_price, j.nid AS jour_nid, j.title AS journal_title, j.issn, j.eissn,j.journal_id, j.subtitle AS jour_subtitle, v.volume_id,v.volume_name AS volume, v.year_id, i.title AS issue, i.month_id ,i.type issue_type, j.subtitle,j.formerly_title, ac.subtitle AS epub_title,a.crossmark_enabled,a.text_mining_urls,a.license_urls,a.created, a.receivedate, a.revisedate, a.acceptdate,js.js_title FROM article a LEFT JOIN article_section ac ON a.is_epub = ac.art_sec_id LEFT JOIN journal_section js ON a.js_id = js.js_id LEFT JOIN article_type at ON a.art_type = at.art_type_id LEFT JOIN issue i ON a.issue_id = i.issue_id LEFT JOIN month m ON m.id = i.month_id LEFT JOIN volume v ON v.volume_id = a.volume_id INNER JOIN year y ON y.id = v.year_id INNER JOIN journal j ON j.journal_id = a.journal_id INNER JOIN publisher p ON p.publisher_id = j.publisher_id WHERE a.article_id=131838
      1.15msalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 117 limit 1
      1.08msalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 117
      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=117) and sj.journal_id!=117 group by `j`.`nid`) as `aggregate_table`
      850μsalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=117) and sj.journal_id!=117 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      720μsalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=117) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      1.5msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=117) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      1.34msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 14. app/Models/Subject.php:220
      • 15. app/Http/Controllers/ArticleController.php:2518
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `keywords` where `article_id` = '131838'
      300μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 131838
      Backtrace
      • 13. app/Models/Keywords.php:43
      • 14. app/Http/Controllers/ArticleController.php:2519
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `article_citation` where `article_id` = '131838'
      6.22msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 131838
      Backtrace
      • 13. app/Models/Article.php:1570
      • 14. app/Http/Controllers/ArticleController.php:2520
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs, CONCAT_WS(' ',au.first_name, IFNULL(CONCAT(' ', au.initials), ''), IFNULL(CONCAT(' ', au.last_name), '')) as authorsmodal , `au`.*, `af`.`ror_id`, `af`.`institution`, `af`.`department`, `af`.`country`, `af`.`city`, `af`.`address`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`article_id` = '131838' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      2.84msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 131838
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ArticleController.php:2533
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      340μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2535
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `subtitle` from `journal` where `continues_publication_journal` = 1
      670μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 117 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      35.93msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 117 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      17.52msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 117 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      4.1msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2071
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select pdf, html, epub, prc from `article_metrics` where `article_id` = 131838 limit 1
      310μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 131838
      Backtrace
      • 14. app/Models/Article.php:744
      • 15. app/Http/Controllers/ArticleController.php:2091
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from content_by_diseases where content_id = 131838 and content_type = 'article' order by status desc limit 1
      410μsalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 216980 limit 1
      330μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 216980
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      280μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'NNA' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      450μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: NNA
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '131838' and content_type = 'a' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      500μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '12681' and content_type = 'i' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      350μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2207
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '3393' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      330μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2231
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1740471496 and j.to_date >= 1740471496 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3393) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1740471496 and j.to_date >= 1740471496 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3393) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1740471496 and j.to_date >= 1740471496 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3393)
      51.38msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2272
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1740471496 and j.to_date >= 1740471496 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12681) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1740471496 and j.to_date >= 1740471496 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12681) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1740471496 and j.to_date >= 1740471496 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12681)
      1.38msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2297
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1740471496 and j.to_date >= 1740471496 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 131838) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1740471496 and j.to_date >= 1740471496 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 131838) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1740471496 and j.to_date >= 1740471496 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 131838)
      940μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2329
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `first_page` < '28' and is_uploaded = 1 and issue_id = 12681 order by cast(first_page as SIGNED) desc limit 1
      720μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 28
      Backtrace
      • 14. app/Models/Article.php:1819
      • 15. app/Http/Controllers/ArticleController.php:2470
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `last_page` > '46' and is_uploaded = 1 and issue_id = 12681 order by cast(first_page as SIGNED) asc limit 1
      640μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 46
      Backtrace
      • 14. app/Models/Article.php:1831
      • 15. app/Http/Controllers/ArticleController.php:2472
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      350μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      320μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 131838 limit 1
      3.89msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 131838
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 117 and `b`.`banner_from_date` <= 1740471496 and `b`.`banner_to_date` >= 1740471496 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.65msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 117
      • 3: 1740471496
      • 4: 1740471496
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 117 and `b`.`banner_from_date` <= 1740471496 and `b`.`banner_to_date` >= 1740471496 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.62msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 117
      • 3: 1740471496
      • 4: 1740471496
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='b69df917916bb9625c3642eab88634f8'
      300μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
    1MultiLanguage.php#?
        _token
        MVmorpT1bsUDQDvS88oesIU2JvuQEnEaY5WqGKEC
        uc_cart_id
        b69df917916bb9625c3642eab88634f8
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/131838" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/131838
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:8 [ "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        []
        
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 25 Feb 2025 08:18:16 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IkowaUpwK1cvVVh2eWVKN0E1TTE4QVE9PSIsInZhbHVlIjoiTWdwNzdUbXNuL0I3YlRBTG9sV29acG01ZU1sTyswbUpjUk5NR0pNMGsrUkFHR1pINGpiVUxtQWJ5UDdJYTU5ay9IRUU4TWtkOG9yUWRJYksxZFc4ZFIydEdxdElwUEdTdzZrN2VTdjMvdExkUVd4WU9jTjV3bERocHBnUnBxU3AiLCJtYWMiOiIyZmUzYjZhNzVmMmJkYzQ5NjRmY2MxYzNkZGU1MjA4NmI0OTFhZjVmZWM2MDllZDQ1Y2ZmNmUxNGNmN2NhNTEzIiwidGFnIjoiIn0%3D; expires=Thu, 27 Feb 2025 20:18:16 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IkowaUpwK1cvVVh2eWVKN0E1TTE4QVE9PSIsInZhbHVlIjoiTWdwNzdUbXNuL0I3YlRBTG9sV29acG01ZU1sTyswbUpjUk5NR0pNMGsrUkFHR1pINGpiVUxtQWJ5UDdJYTU5ay9IRUU4T" 1 => "alphaeurekaselectnet_session=eyJpdiI6Ilp3THB1ZkxYK3duQ3Y4eVp6NGNNcEE9PSIsInZhbHVlIjoiSzZONjV1TlhidUNORGJjT05iMUZPTml1SG9EVC9PbG9DMWVQU0JoRm9JY3kxVk1NdWkrOXpRNGlzVHNlTVNZWUNkT3U4U2trbllZUTg1L3RoMjJWY2lGRGRtZEtJcUYwQXNGVnpEdmV5OFVQaHNZQ3FBeWdxYk5HRGRXcmJBUUgiLCJtYWMiOiI4NDJjYjcwMmUyMTIwNjNjZjE4YzMwNGY1Mjc4OWZiNzEwNTBmZDVjOTBkYTg1YWRmNjM1YmY2ZjkzODE0OTcyIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6Ilp3THB1ZkxYK3duQ3Y4eVp6NGNNcEE9PSIsInZhbHVlIjoiSzZONjV1TlhidUNORGJjT05iMUZPTml1SG9EVC9PbG9DMWVQU0JoRm9JY3kxVk1NdWkrOXpRNGl" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IkowaUpwK1cvVVh2eWVKN0E1TTE4QVE9PSIsInZhbHVlIjoiTWdwNzdUbXNuL0I3YlRBTG9sV29acG01ZU1sTyswbUpjUk5NR0pNMGsrUkFHR1pINGpiVUxtQWJ5UDdJYTU5ay9IRUU4TWtkOG9yUWRJYksxZFc4ZFIydEdxdElwUEdTdzZrN2VTdjMvdExkUVd4WU9jTjV3bERocHBnUnBxU3AiLCJtYWMiOiIyZmUzYjZhNzVmMmJkYzQ5NjRmY2MxYzNkZGU1MjA4NmI0OTFhZjVmZWM2MDllZDQ1Y2ZmNmUxNGNmN2NhNTEzIiwidGFnIjoiIn0%3D; expires=Thu, 27-Feb-2025 20:18:16 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IkowaUpwK1cvVVh2eWVKN0E1TTE4QVE9PSIsInZhbHVlIjoiTWdwNzdUbXNuL0I3YlRBTG9sV29acG01ZU1sTyswbUpjUk5NR0pNMGsrUkFHR1pINGpiVUxtQWJ5UDdJYTU5ay9IRUU4T" 1 => "alphaeurekaselectnet_session=eyJpdiI6Ilp3THB1ZkxYK3duQ3Y4eVp6NGNNcEE9PSIsInZhbHVlIjoiSzZONjV1TlhidUNORGJjT05iMUZPTml1SG9EVC9PbG9DMWVQU0JoRm9JY3kxVk1NdWkrOXpRNGlzVHNlTVNZWUNkT3U4U2trbllZUTg1L3RoMjJWY2lGRGRtZEtJcUYwQXNGVnpEdmV5OFVQaHNZQ3FBeWdxYk5HRGRXcmJBUUgiLCJtYWMiOiI4NDJjYjcwMmUyMTIwNjNjZjE4YzMwNGY1Mjc4OWZiNzEwNTBmZDVjOTBkYTg1YWRmNjM1YmY2ZjkzODE0OTcyIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6Ilp3THB1ZkxYK3duQ3Y4eVp6NGNNcEE9PSIsInZhbHVlIjoiSzZONjV1TlhidUNORGJjT05iMUZPTml1SG9EVC9PbG9DMWVQU0JoRm9JY3kxVk1NdWkrOXpRNGl" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "MVmorpT1bsUDQDvS88oesIU2JvuQEnEaY5WqGKEC" "uc_cart_id" => "b69df917916bb9625c3642eab88634f8" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/131838" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 08:18:16GET/article/131838414361