Transdermal delivery of insulin via microneedles

Journal of Biomedical Nanotechnology

Volumn 10, Issue 9, 2014, Pages 2244-2260

  Narayan, Roger J ^a  

^a NORTH CAROLINA STATE UNIVERSITY   (United States)

Author keywords

Diabetes mellitus; Insulin; Intradermal delivery; Microneedle; Nanomaterials; Transdermal delivery

Indexed keywords

ARTIFICIAL ORGANS; DRUG DELIVERY; NANOSTRUCTURED MATERIALS; NEEDLES;

ARTIFICIAL PANCREAS; DIABETES MELLITUS; DRUG DELIVERY DEVICES; INSULIN-DEPENDENT DIABETES MELLITUS; INTRADERMAL DELIVERY; MICRONEEDLES; TRANSDERMAL DELIVERY; TYPE 1 DIABETES MELLITUS;

INSULIN;

FLUORESCEIN ISOTHIOCYANATE; GLUCOSE; HUMAN INSULIN; INSULIN; INSULIN LISPRO; INSULIN ZINC SUSPENSION; ISOPHANE INSULIN; NANOMATERIAL; RECOMBINANT HUMAN INSULIN;

BLOOD GLUCOSE MONITORING; DIFFUSION; DRUG DELIVERY SYSTEM; GLUCOSE BLOOD LEVEL; HUMAN; INSULIN PUMP; MICRONEEDLE; MICROTECHNOLOGY; NONHUMAN; PARTICLE SIZE; REVIEW; SKIN PERMEABILITY; STREPTOZOTOCIN-INDUCED DIABETES MELLITUS; TRANSDERMAL PATCH; ANIMAL; DEVICES; INTRADERMAL DRUG ADMINISTRATION; MICROINJECTION; NEEDLE;

ADMINISTRATION, CUTANEOUS; ANIMALS; DRUG DELIVERY SYSTEMS; HUMANS; INSULIN; MICROINJECTIONS; NEEDLES;

EID: 84904863848     PISSN: 15507033     EISSN: 15507041     Source Type: Journal    
DOI: 10.1166/jbn.2014.1976     Document Type: Review

References (102)

1. J. A. Bluestone, K. Herold, and G. Eisenbarth, Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature 464, 1293 (2010).
2. W. Rodger, Insulin-dependent (type I) diabetes mellitus. Can. Med. Assoc. J. 145, 1227 (1991).
3. K. M. Paknikar and A. Jeremic, Discovery of the cell secretion machinery. J. Biomed. Nanotechnol. 3, 218 (2007).
4. L. Jönsson, I. Hallström, and A. Lundqvist, "The logic of care" - Parents' perceptions of the educational process when a child is newly diagnosed with type 1 diabetes. BMC Pediatr. 12, 165 (2012).
5. Centers for Disease Control and Prevention. National Diabetes Fact Sheet: National Estimates and General Information on Diabetes and Prediabetes in the United States, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Atlanta, GA (2011).
6. Centers for Disease Control and Prevention. National Diabetes Fact Sheet, 2011. Centers for Disease Control and Prevention, US Department of Health and Human Services, Atlanta, GA (2011).
7. A. S. Krolewski, E. J. Kosinski, J. H. Warram, O. S. Leland, E. J. Busick, A. C. Asmal, L. I. Rand, A. R. Christlieb, R. F. Bradley, and C. R. Kahn, Magnitude and determinants of coronary artery disease in juvenile onset, insulin-dependent diabetes mellitus. Am. J. Cardiol. 59, 750 (1987).
8. W. K. Waldhausl, The physiological basis of insulin treatment clinical aspects. Diabetologia 29, 837 (1986).
9. Y. L. Wu, Y. P. Ding, J. Gao, Y. Tanaka, and W. Zhang, Risk factors and primary prevention trials for type 1 diabetes. Int. J. Biol. Sci. 9, 666 (2013).
10. The Diabetes Control and Complications Trial Research Group, The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. New Engl. J. Med. 329, 683 (1993).
11. J. C. Birchall, Microneedle array technology: The time is right but is the science ready? Expert Rev. Med. Devices 3, 1 (2006).
12. J. J. Escobar-Chávez, D. Bonilla-Martínez, M. A. Villegas-González, E. Molina-Trinidad, N. Casas-Alancaster, and A. L. Revilla-Vázquez, Microneedles: A valuable physical enhancer to increase transdermal drug delivery. J. Clin. Pharmacol. 51, 964 (2011).
13. P. V. Bharatam and S. Sundriyal, Molecular electrostatic potentials in the design of dendrimers for the delivery of glitazones. J. Nanosci. Nanotechnol. 6, 3277 (2006).
14. N. Zhang, Q. N. Ping, G. Huang, X. Z. Han, Y. Cheng, and W. F. Xu, Transport characteristics of wheat germ agglutinin-modified insulin-liposomes and solid lipid nanoparticles in a perfused rat intestinal model, J. Nanosci. Nanotechnol. 6, 2959 (2006).
15. I. T. Degim, B. Gumusel, Z. Degim, T. Ozcelikay, A. Tay, and S. Guner, Oral administration of liposomal insulin, J. Nanosci. Nanotechnol. 6, 2945 (2006).
16. M. G. Li, W. L. Lu, J. C. Wang, X. Zhang, H. Zhang, X. Q. Wang, C. S. Wu, and Q. Zhang, Preparation and characterization of insulin nanoparticles employing chitosan and poly(methyl-methacrylate/methylmethacrylic acid) copolymer. J. Nanosci. Nanotechnol. 6, 2874 (2006).
17. A. Mukerjee and V. Pruthi, Oral insulin delivery by polymeric nanospheres. J. Biomed. Nanotechnol. 3, 68 (2007).
18. B. Sarmento, A. J. Ribeiro, F. Veiga, D. C. Ferreira, and R. J. Neufeld, Insulin-loaded nanoparticles are prepared by alginate ionotropic pre-gelation followed by chitosan polyelectrolyte complexation. J. Nanosci. Nanotechnol. 7, 2833 (2007).
19. R. Bi and N. Zhang, Liposomes as a carrier for pulmonary delivery of peptides and proteins. J. Biomed. Nanotechnol. 3, 332 (2007).
20. D. V. Ratnam, G. Chandraiah, K. Sonaje, B. Viswanad, V. Bhardwaj, P. Ramarao, and M. N. V. Ravikumar, A potential therapeutic strategy for diabetes and its complications in the form of co-encapsulated antioxidant nanoparticles (NanoCAPs) of ellagic acid and coenzyme Q(10): Preparation and evaluation in streptozotocin induced diabetic rats. J. Biomed. Nanotechnol. 4, 33 (2008).
21. K. Sato, D. Kodama, Y. Endo, and J. Anzai, Preparation of insulin-containing microcapsules by a layer-by-layer deposition of concanavalin A and glycogen. J. Nanosci.Nanotechnol. 9, 386 (2009).
22. R. Bi, W. Shao, Q. Wang, and M. Zhang, Solid lipid nanoparticles as insulin inhalation carriers for enhanced pulmonary delivery. J. Biomed. Nanotechnol. 5, 84 (2009).
23. M. J. Santander-Ortega, D. Bastos-Gonzalez, J. L. Ortega-Vinuesa, and M. J. Alonso, Insulin-loaded plga nanoparticles for oral administration: An in vitro physico-chemical characterization. J. Nanosci. Nanotechnol. 5, 45 (2009).
24. H. R. Lin, W. J. Chen, and M. H. Ling, pH-sensitive dioctadecylamine-501 polymeric micelles for delivery of insulin. J. Nanosci. Nanotechnol. 11, 1823 (2011).
25. A. Manosroi, N. Khositsuntiwong, C. Komno, W. Manosroi, R. G. Werner, and J. Manosoi, Chemical stability and cytotoxicity of human insulin loaded in cationic dppc/cta/ddab liposomes. J. Biomed. Nanotechnol. 7, 308 (2011).
26. R. Bakhshi, Z. Ahmad, M. Soric, E. Stride, and M. Edirisinghe, Nanoparticle delivery systems formed using electrically sprayed co-flowing excipients and active agent. J. Biomed. Nanotechnol. 7, 782 (2011).
27. Q. Y. Zhang, N. He, L. Zhang, F. Zhu, Q. X. Chen, Y. Qin, Z. R. Zhang, Q. Zhang, S. Wang, and Q. He, The in vitro and in vivo study on self-nanoemulsifying drug delivery system (snedds) based on insulin-phospholipid complex. J. Biomed. Nanotechnol. 8, 90 (2012).
28. X. Y. Yang, Y. J. Liu, C. X. Liu, and N. Zhang, Biodegradable solid lipid nanoparticle flocculates for pulmonary delivery of insulin. J. Biomed. Nanotechnol. 8, 834 (2012).
29. R. Shelma and C. P. Sharma, In vitro cell culture evaluation and in vivo efficacy of amphiphilic chitosan for oral insulin delivery. J. Biomed. Nanotechnol. 9, 167 (2013).
30. Z. H. Zhang, S. Abbad, R. R. Pan, A. Y. Waddad, L. L. Hou, H. X. Lv, and J. P. Zhou, N -octyl-N -arginine chitosan micelles as an oral delivery system of insulin. J. Biomed. Nanotechnol. 9, 590 (2013).
31. T. A. Sonia and C. P. Sharma, In vitro evaluation of thiolated polydimethylaminoethylmethacrylate hydrogel sub-microparticles for oral insulin delivery. J. Biomed. Nanotechnol. 9, 590 (2013).
32. T. M. de Araujo, Z. Teixeira, H. C. Barbosa-Sampaio, L. F. Rezende, A. C. Boschero, N. Duran, and N. F. Hoehr, Insulin-loaded poly(epsilon-caprolactone) nanoparticles: Efficient, sustained and safe insulin delivery system. J. Biomed. Nanotechnol. 9, 1098 (2013).
33. T. A. Sonia and C. P. Sharma, pH sensitive thiolated cationic hydrogel for oral insulin delivery. J. Biomed. Nanotechnol. 10, 642 (2014).
34. P. Khanna, J. A. Strom, J. I. Malone, and S. Bhansali, Microneedle-based automated therapy for diabetes mellitus. J. Diabetes Sci. Technol. 2, 1122 (2008).
35. S. H. Bariya, M. C. Gohel, T. A. Mehta, and O. P. Sharma, Microneedles: An emerging transdermal drug delivery system. J. Pharm. Pharmacol. 64, 11 (2011).
36. M. S. Gerstel and V. A. Place, Drug delivery device, US Patent 3,964,482 (1976).
37. R. J. Pettis and A. J. Harvey, Microneedle delivery: Clinical studies and emerging medical applications. Ther. Deliv. 3, 357 (2012).
38. Y. C. Kim, J. H. Park, and M. R. Prausnitz, Microneedles for drug and vaccine delivery. Adv. Drug Deliver. Rev. 64, 1547 (2012).
39. T. M. Tuan-Mahmood, M. T. McCrudden, B. M. Torrisi, E. McAlister, M. J. Garland, T. R. Singh, and R. F. Donnelly, Microneedles for intradermal and transdermal drug delivery. Eur. J. Pharm. Sci. 50, 623 (2013).
40. A. Arora, M. Prausnitz, and S. Mitragotri, Micro-scale devices for transdermal drug delivery. Int. J. Pharm. 364, 227 (2008).
41. A. El-Laboudi, N. S. Oliver, A. Cass, and D. Johnston, Use of microneedle array devices for continuous glucose monitoring: A review. Diabetes Technol. Ther. 15, 101 (2013).
42. M. R. Prausnitz and R. Langer, Transdermal drug delivery. Nat. Biotechnol. 26, 1261 (2008).
43. S. Kaushik, A. H. Hord, D. D. Denson, D. V. McAllister, S. Smitra, M. G. Allen, and M. R. Prausnitz, Lack of pain associated with microfabricated microneedles. Anesth. Analg. 92, 502 (2001).
44. H. S. Gill and M. R. Prausnitz, Does needle size matter? J. Diabetes Sci. Technol. 1, 725 (2007).
45. J. C. Birchall, R. Clemo, A. Anstey, and D. N. John, Microneedles in clinical practice-An exploratory study into the opinions of healthcare professionals and the public. Pharmaceut. Res. 28, 95 (2011).
46. D. Trebotich, J. D. Zahn, and D. Liepmann, Complex fluid dynamics in BioMEMS devices: Modeling of microfabricated microneedles, ICCN 2002: International Conference on Computational Nanoscience and Nanotechnology, San Juan, Puerto Rico (2002), pp. 20-23.
47. H. J. G. E. Gardeniers, R. Luttge, E. J. W. Berenschot, M. J. de Boer, S. Y. Yeshurun, M. Hefetz, R. van't Oever, and A. van den Berg, Silicon micromachined hollow microneedles for transdermal liquid transport. IEEE J. Microelectromech. Syst. 12, 855 (2003).
48. D. V. McAllister, P. M. Wang, S. P. Davis, J. H. Park, P. J. Canatella, M. G. Allen, and M. R. Prausnitz, Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: Fabrication methods and transport studies. Proc. Natl. Acad. Sci. USA 100, 13755 (2003).
49. W. Martanto, S. P. Davis, N. R. Holiday, J. Wang, H. S. Gill, and M. R. Prausnitz, Transdermal delivery of insulin using microneedles in vivo, Proceedings of the 30th International Symposium on Controlled Release of Bioactive Materials (2003).
50. M. R. Prausnitz, Microneedles for transdermal drug delivery. Adv. Drug Deliver. Rev. 56, 581 (2004).
51. W. Martanto, S. P. Davis, N. R. Holiday, J. Wang, H. S. Gill, and M. R. Prausnitz, Transdermal delivery of insulin using microneedles in vivo. Pharmaceut. Res. 21, 947 (2004).
52. P. Zhang and G. A. Jullien, Microneedle arrays for drug delivery and fluid extraction. Proc. 2005 Int. Conf. MEMS, NANO Smart Syst., Banff, Alberta, CA, IEEE Conference, Los Alamitos, CA, USA (2005), pp. 392-395.
53. M. A. Teo, C. Shearwood, K. C. Ng, J. Lu, and S. Moochhala, In vitro and in vivo characterization of MEMS microneedles. Biomed. Microdev. 7, 47 (2005).
54. S. P. Davis, W. Martanto, M. G. Allen, and M. R. Prausnitz, Hollow metal microneedles for insulin delivery to diabetic rats. IEEE Trans. Biomed. Eng. 52, 909 (2005).
55. J. D. Zahn, Y. C. Hsieh, and M. Yang, Components of an integrated microfluidic device for continuous glucose monitoring with responsive insulin delivery. Diabetes Tech. Therapeut. 7, 536 (2005).
56. N. Nakanishi, H. Yamamoto, K. Tsuchiya, Y. Uetsuji, and E. Nakamachi, Development of wearable medical device for Bio-MEMS. Proc. SPIE: BioMEMS Nanotechnol. II 6036, 168 (2006).
57. P. M. Wang, M. Cornwell, J. Hill, and M. R. Prausnitz, Precise microinjection into skin using hollow microneedles. J. Invest. Dermatol. 126, 1080 (2006).
58. M. Hompesch, N. G. Harvey, L. Heinemann, B. H. Ginsberg, C. Kapitza, and R. J. Pettis, Intra-dermal insulin Lispro application with a new microneedle delivery system led to a substantially more rapid insulin absorption than subcutaneous injection. Diabetologia 49, 620 (2006).
59. B. Ma, S. Liu, Z. Gan, G. Liu, X. Cai, H. Zhang, and Z. Yang, A PZT insulin pump integrated with a silicon microneedle array for transdermal drug delivery. Microfluid. Nanofluid. 2, 417 (2006).
60. Y. Ito, E. Hagiwara, A. Saeki, N. Sugioka, and K. Takada, Feasibility of microneedles for percutaneous absorption of insulin. Eur. J. Pharm. Sci. 29, 82 (2006).
61. Y. G. Lv, J. Liu, Y. H. Gao, and B. Xu, Modeling of transdermal drug delivery with a microneedle array. J. Micromech. Microeng. 16, 2492 (2006).
62. C. R. Lee, M. S. Kim, H. B. Lee, H. K. Lee, J. M. Rhee, and G. S. Khang, The effect of molecular weight of drugs on transdermal delivery system using microneedle device. Key Eng. Mater. 342-343, 945 (2007).
63. Y. Ito, E. Hagiwara, A. Saeki, N. Sugioka, and K. Takada, Sustained-release self-dissolving micropiles for percutaneous absorption of insulin in mice. J. Drug Target. 15, 323 (2007).
64. L. Nordquist, N. Roxhed, P. Griss, and G. Stemme, Novel microneedle patches for active insulin delivery are efficient in maintaining glycaemic control: An initial comparison with subcutaneous administration. Pharmaceut. Res. 24, 1381 (2007).
65. H. S. Gill and M. R. Prausnitz, Coating formulations for microneedles. Pharmaceut. Res. 24, 1369 (2007).
66. N. Roxhed, B. Samel, L. Nordquist, P. Griss, and G. Stemme, Painless drug delivery through microneedle-based transdermal patches featuring active infusion. IEEE Trans. Biomed. Eng. 55, 1063 (2008).
67. B. Al-Qallaf and D. B. Das, Optimization of square microneedle arrays for increasing drug permeability in skin. Chem. Eng. Sci. 63, 2523 (2008).
68. A. Kabata, K. Okamura, H. Suzuki, Y. Kishigami, M. Kikuchi, and M. Haga, Prototype micropump for insulin administration based on electrochemical bubble formation. J. Pharm. Sci. 97, 5037 (2008).
69. A. Davidson, B. Al-Qallaf, and D. B. Das, Transdermal drug delivery by coated microneedles: Geometry effects on effective skin thickness and drug permeability. Chem. Eng. Res. Des. 86, 1196 (2008).
70. J. Gupta, E. I. Felner, and M. R. Prausnitz, Minimally invasive insulin delivery in subjects with Type 1 diabetes using hollow microneedles. Diabetes Technol. Ther. 11, 329 (2009).
71. N. G. Harvey, L. Heinemann, L. J. Hirsch, D. E. Sutter, R. J. Pettis, L. Nosek, and C. Kapitza, Microneedle-based intradermal injection of Lispro or human regular insulin accelerates insulin uptake and reduces post-prandial glycaemia. Diabetologia 52, S378 (2009).
72. H. Chen, H. Zhu, J. Zheng, D. Mou, J. Wan, J. Zhang, T. Shi, Y. Zhao, H. Xu, and X. Yang, Iontophoresis-driven penetration of nanovesicles through microneedle-induced skin microchannels for enhancing transdermal delivery of insulin. J. Control Release 139, 63 (2009).
73. B. Al-Qallaf, D. B. Das, and A. Davidson, Transdermal drug delivery by coated microneedles: Geometry effects on drug concentration in blood. Asia Pac. J. Chem. Eng. 4, 845 (2009).
74. K. Lee, H. C. Lee, D. S. Lee, and H. Jung, Drawing lithography: Three-dimensional fabrication of an ultrahigh-aspect-ratio microneedle. Adv. Mater. 22, 483 (2010).
75. C. P. Zhou, Y. L. Liu, H. L. Wang, P. X. Zhang, and J. L. Zhang, Transdermal delivery of insulin using microneedle rollers in vivo. Int. J. Pharm. 392, 127 (2010).
76. Y. Wu, Y. Gao, G. Qin, S. Zhang, Y. Qiu, F. Li, and B. Xu, Sustained release of insulin through skin by intradermal microdelivery system. Biomed. Microdev. 12, 665 (2010).
77. A. J. Harvey, S. A. Kaestner, D. E. Sutter, N. G. Harvey, J. A. Mikszta, and R. J. Pettis, Microneedle-based intradermal delivery enables rapid lymphatic uptake and distribution of protein drugs. Pharmaceut. Res. 28, 107 (2011).
78. J. Gupta, E. I. Felner, and M. R. Prausnitz, Rapid pharmacokinetics of intradermal insulin administered using microneedles in type 1 diabetes subjects. Diabetes Technol. Ther. 13, 451 (2011).
79. R. J. Pettis, B. Ginsberg, L. Hirsch, D. Sutter, S. Keith, E. McVey, N. G. Harvey, M. Hompesch, L. Nosek, C. Kapitza, and L. Heinemann, Intradermal microneedle delivery of insulin Lispro achieves faster insulin absorption and insulin action than subcutaneous injection. Diabetes Technol. Ther. 13, 435 (2011).
80. R. J. Pettis, L. Hirsch, C. Kapitza, L. Nosek, U. Hövelmann, H. J. Kurth, D. E. Sutter, N. G. Harvey, and L. Heinemann, Microneedle-based intradermal versus subcutaneous administration of regular human insulin or insulin lispro: Pharmacokinetics and postprandial glycemic excursions in patients with type 1 diabetes. Diabetes Technol. Ther. 13, 443 (2011).
81. K. Migalska, D. I. Morrow, M. J. Garland, R. Thakur, A. D. Woolfson, and R. F. Donnelly, Laser-engineered dissolving microneedle arrays for transdermal macromolecular drug delivery. Pharmaceut. Res. 28, 1919 (2011).
82. S. Yang, Y. Feng, L. Zhang, N. Chen, W. Yuan, and T. Jin, A scalable fabrication process of polymer microneedles. Int. J. Nanomed. 7, 1415 (2012).
83. G. Qin, Y. Gao, Y. Wu, S. Zhang, Y. Qiu, F. Li, and B. Xu, Simultaneous basal-bolus delivery of fast-acting insulin and its significance in diabetes management. Nanomed. 8, 221 (2012).
84. M. J. Garland, E. Caffarel-Salvador, K. Migalska, A. D. Woolfson, and R. F. Donnelly, Dissolving polymeric microneedle arrays for electrically assisted transdermal drug delivery. J. Control Release 159, 52 (2012).
85. E. McVey, L. Hirsch, D. E. Sutter, C. Kapitza, S. Dellweg, J. Clair, K. Rebrin, K. Judge, and R. J. Pettis, Pharmacokinetics and postprandial glycemic excursions following insulin Lispro delivered by intradermal microneedle or subcutaneous infusion. J. Diabetes Sci. Technol. 6, 743 (2012).
86. S. Liu, M. N. Jin, Y. S. Quan, F. Kamiyama, H. Katsumi, T. Sakane, and A. Yamamoto, The development and characteristics of novel microneedle arrays fabricated from hyaluronic acid, and their application in the transdermal delivery of insulin. J. Control Release 161, 933 (2012).
87. H. Y. Poon, W. K. Wong, L. Y. Chau, W. Han, S. M. Kwan, M. H. Lee, H. L. Chow, and K. L. Yeung, Design of zeolite microneedles for regulated transdermal drug delivery. Abstr. Pap. Am. Chem. Soc. 244, 395 (2012).
88. Y. Ito, T. Nakahigashi, N. Yoshimoto, Y. Ueda, N. Hamasaki, and K. Takada, Transdermal insulin application system with dissolving microneedles. Diabetes Technol. Ther. 14, 891 (2012).
89. Y. Ito, M. Hirono, K. Fukushima, N. Sugioka, and K. Takada, Two-layered dissolving microneedles formulated with intermediate-acting insulin. Int. J. Pharm. 436, 387 (2012).
90. Y. Qiu, G. Qin, S. Zhang, Y. Wu, B. Xu, and Y. Gao, Novel lyophilized hydrogel patches for convenient and effective administration of microneedle-mediated insulin delivery. Int. J. Pharm. 437, 51 (2012).
91. R. F. Donnelly, T. R. Singh, M. J.Garland, K. Migalska, R. Majithiya, C. M. McCrudden, P. L. Kole, T. M. Mahmood, H. O. McCarthy, and A. D. Woolfson, Hydrogel-forming microneedle arrays for enhanced transdermal drug delivery. Adv. Funct. Mater. 22, 4879 (2012).
92. S. Keith, E. McVey, D. Sutter, C. Kapitza, L. Nosek, K. Judge, and R. J. Pettis, Pharmacokinetics and feasibility of insulin Lispro microneedle-based intradermal (id) infusion. Diabetes Tech. Therapeut. 15, A85 (2013).
93. Y. Qiu, Y. Gao, S. Zhang, L. Guo, J. Chen, and B. Xu, Immunological effects of microneedle-mediated insulin delivery: Preliminary rat studies. Int. J. Pharm. 444, 103 (2013).
94. J. D. Kim, M. Kim, H. Yang, K. Lee, and H. Jung, Droplet-born air blowing: Novel dissolving microneedle fabrication. J. Control Release 170, 430 (2013).
95. J. J. Norman, M. R. Brown, N. A. Raviele, M. R. Prausnitz, and E. I. Felner, Faster pharmacokinetics and increased patient acceptance of intradermal insulin delivery using a single hollow microneedle in children and adolescents with type 1 diabetes. Pediatr. Diabetes 14, 459 (2013).
96. M. H. Ling and M. C. Chen, Dissolving polymer microneedle patches for rapid and efficient transdermal delivery of insulin to diabetic rats. Acta Biomater. 9, 8952 (2013).
97. C. L. Stevenson, J. T. Santini, and R. Langer, Reservoir-based drug delivery systems utilizing microtechnology. Adv. Drug Deliv. Rev. 64, 1590 (2012).
98. P. C. Butler and R. A. Rizza, Regulation of carbohydrate metabolism and response to hypoglycemia. Endocrin. Metab. Clin. 18, 1 (1989).
99. A. Misra and S. Bhardwaj, Obesity and the metabolic syndrome in developing countries: Focus on South Asians. Nestle Nutr. Inst. Workshop Ser. 78, 133 (2014).
100. S. Kumpatla, H. Kothandan, S. Tharkar, and V. Viswanathan, The costs of treating long-term diabetic complications in a developing country: A study from India. J. Assoc. Physicians India 61, 102 (2013).
101. S. A. Schellini, G. M. Carvalho, F. S. Rendeiro, C. R. Padovani, and F. E. Hirai, Prevalence of diabetes and diabetic retinopathy in a Brazilian population. Ophthalmic Epidemiol. 21, 33 (2014).
102. L. M. Strambini, A. Longo, A. Diligenti, and G. Barillaro, A minimally invasive microchip for transdermal injection/sampling applications. Lab Chip 12, 3370 (2012).