Abstract

Fabrication and characterization of an optically monitored hybrid patch for local administration of drugs, based on polymeric micro-needles and a porous silicon free-standing membrane, are reported. The micro-needles are realized by an innovative photolithographic approach that allows fine tuning of geometrical parameters, using polyethylene glycol and a commercial photo-catalyzer. The porous silicon multilayer not only increases the storage of a relevant amount of the drug, but also offers a continuous, naked-eye monitoring of the drug delivery process. As a proof-of-concept experiment, we report our results on the release of a dye molecule (fluorescein, 332 Da) in a phosphate saline buffer.

© 2016 Optical Society of America

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  1. S. Henry, D. V. McAllister, M. G. Allen, and M. R. Prausnitz, “Microfabricated Microneedles: A Novel Approach to Transdermal Drug Delivery,” J. Pharm. Sci. 87(8), 922–925 (1998).
    [Crossref] [PubMed]
  2. E. V. Mukerjee, S. D. Collins, R. R. Isseroff, and R. L. Smith, “Microneedle array for transdermal biological fluid extraction and in situ analysis,” Sens. Actuators A Phys. 114(2-3), 267–275 (2004).
    [Crossref]
  3. P. R. Miller, S. A. Skoog, T. L. Edwards, D. M. Lopez, D. R. Wheeler, D. C. Arango, X. Xiao, S. M. Brozik, J. Wang, R. Polsky, and R. J. Narayan, “Multiplexed Microneedle-based Biosensor Array for Characterization of Metabolic Acidosis,” Talanta 88, 739–742 (2012).
    [Crossref] [PubMed]
  4. M. R. Prausnitz and R. Langer, “Transdermal drug delivery,” Nat. Biotechnol. 26(11), 1261–1268 (2008).
    [Crossref] [PubMed]
  5. 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(2), 502–504 (2001).
    [Crossref] [PubMed]
  6. M. R. Prausnitz, “Reversible skin permeabilization for transdermal delivery of macromolecules,” Crit. Rev. Ther. Drug Carrier Syst. 14(4), 455–483 (1997).
    [Crossref] [PubMed]
  7. E. M. Cahill and E. D. O’Cearbhaill, “Toward Biofunctional Microneedles for Stimulus Responsive Drug Delivery,” Bioconjug. Chem. 26(7), 1289–1296 (2015).
    [Crossref] [PubMed]
  8. L. Ventrelli, L. Marsilio Strambini, and G. Barillaro, “Microneedles for Transdermal Biosensing: Current Picture and Future Direction,” Adv. Healthc. Mater. 4(17), 2606–2640 (2015).
    [Crossref] [PubMed]
  9. N. Wilke, A. Mulcahy, S.-R. Ye, and A. Morrissey, “Process optimization and characterization of silicon microneedles fabricated by wet etch technology,” Microelectronics J. 36(7), 650–656 (2005).
    [Crossref]
  10. F. Chabri, K. Bouris, T. Jones, D. Barrow, A. Hann, C. Allender, K. Brain, and J. Birchall, “Microfabricated silicon microneedles for nonviral cutaneous gene delivery,” Br. J. Dermatol. 150(5), 869–877 (2004).
    [Crossref] [PubMed]
  11. M. B. Mellott, K. Searcy, and M. V. Pishko, “Release of protein from highly cross-linked hydrogels of poly(ethylene glycol) diacrylate fabricated by UV polymerization,” Biomaterials 22(9), 929–941 (2001).
    [Crossref] [PubMed]
  12. G. Valdés-Ramírez, J. R. Windmiller, J. C. Claussen, A. G. Martinez, F. Kuralay, M. Zhou, N. Zhou, R. Polsky, P. R. Miller, R. Narayan, and J. Wang, “Multiplexed and switchable release of distinct fluids from microneedle platforms via conducting polymer nanoactuators for potential drug delivery,” Sens. Actuators B Chem. 161(1), 1018–1024 (2012).
    [Crossref] [PubMed]
  13. M. W. Ashraf, S. Tayyaba, and N. Afzulpurkar, “Micro Electromechanical Systems (MEMS) Based Microfluidic Devices for Biomedical Applications,” Int. J. Mol. Sci. 12(6), 3648–3704 (2011).
    [Crossref] [PubMed]
  14. J. L. Tan, J. Tien, D. M. Pirone, D. S. Gray, K. Bhadriraju, and C. S. Chen, “Cells lying on a bed of microneedles: An approach to isolate mechanical force,” Proc. Natl. Acad. Sci. U.S.A. 100(4), 1484–1489 (2003).
    [Crossref] [PubMed]
  15. R. Vecchione, S. Coppola, E. Esposito, C. Casale, V. Vespini, S. Grilli, P. Ferraro, and P. A. Netti, “Electro-Drawn Drug-Loaded Biodegradable Polymer Microneedles as a Viable Route to Hypodermic Injection,” Adv. Funct. Mater. 24(23), 3515–3523 (2014).
    [Crossref]
  16. R. F. Donnelly, T. R. R. Singh, M. J. Garland, K. Migalska, R. Majithiya, C. M. McCrudden, P. L. Kole, T. M. T. Mahmood, H. O. McCarthy, and A. D. Woolfson, “Hydrogel-forming microneedle arrays for enhanced transdermal drug delivery,” Adv. Funct. Mater. 22(23), 4879–4890 (2012).
    [Crossref] [PubMed]
  17. J. R. Henstock, L. T. Canham, and S. I. Anderson, “Silicon: The evolution of its use in biomaterials,” Acta Biomater. 11, 17–26 (2015).
    [Crossref] [PubMed]
  18. L. De Stefano, L. Moretti, I. Rendina, and A. M. Rossi, “Time-resolved sensing of chemical species in porous silicon optical microcavity,” Sens. Actuators B Chem. 100(1-2), 168–172 (2004).
    [Crossref]
  19. I. Rendina, I. Rea, L. Rotiroti, and L. De Stefano, “Porous Silicon Based Optical Biosensors and Biochips,” Physica E 38(1-2), 188–192 (2007).
    [Crossref]
  20. L. De Stefano, M. Rossi, M. Staiano, G. Mamone, A. Parracino, L. Rotiroti, I. Rendina, M. Rossi, and S. D’Auria, “Glutamine-binding protein from Escherichia coli specifically binds a wheat gliadin peptide allowing the design of a new porous silicon-based optical biosensor,” J. Proteome Res. 5(5), 1241–1245 (2006).
    [Crossref] [PubMed]
  21. L. De Stefano, I. Rea, P. Giardina, A. Armenante, and I. Rendina, “Protein modified porous silicon nanostructures,” Adv. Mater. 20(8), 1529–1533 (2008).
    [Crossref]
  22. P. Dardano, A. Caliò, V. Di Palma, M. F. Bevilacqua, A. Di Matteo, and L. De Stefano, “Photolithographic approaches to polymeric microneedles array fabrication for biomedical applications,” Materials (Basel) 8(12), 8661–8673 (2015).
    [Crossref]
  23. R. F. Donnelly, T. R. Raj Singh, and A. D. Woolfson, “Microneedle-based drug delivery systems: Microfabrication, drug delivery, and safety,” Drug Deliv. 17(4), 187–207 (2010).
    [Crossref] [PubMed]
  24. E. Larrañeta, J. Moore, E. M. Vicente-Pérez, P. González-Vázquez, R. Lutton, A. D. Woolfson, and R. F. Donnelly, “A proposed model membrane and test method for microneedle insertion studies,” Int. J. Pharm. 472(1-2), 65–73 (2014).
    [Crossref] [PubMed]
  25. H. Li, Y. Yu, S. Faraji Dana, B. Li, C.-Y. Lee, and L. Kang, “Novel engineered systems for oral, mucosal and transdermal drug delivery,” J. Drug Target. 21(7), 611–629 (2013).
    [Crossref] [PubMed]
  26. Prof. L. T. Canham, pSiMedica Ltd, Malvern Hills Science Park, Malvern, Worcerstershire, WR14 35Z, UK, private communication.
  27. J. S. Kochhar, W. X. S. Lim, S. Zou, W. Y. Foo, J. Pan, and L. Kang, “Microneedle Integrated Transdermal Patch for Fast Onset and Sustained Delivery of Lidocaine,” Mol. Pharm. 10(11), 4272–4280 (2013).
    [Crossref] [PubMed]

2015 (4)

E. M. Cahill and E. D. O’Cearbhaill, “Toward Biofunctional Microneedles for Stimulus Responsive Drug Delivery,” Bioconjug. Chem. 26(7), 1289–1296 (2015).
[Crossref] [PubMed]

L. Ventrelli, L. Marsilio Strambini, and G. Barillaro, “Microneedles for Transdermal Biosensing: Current Picture and Future Direction,” Adv. Healthc. Mater. 4(17), 2606–2640 (2015).
[Crossref] [PubMed]

J. R. Henstock, L. T. Canham, and S. I. Anderson, “Silicon: The evolution of its use in biomaterials,” Acta Biomater. 11, 17–26 (2015).
[Crossref] [PubMed]

P. Dardano, A. Caliò, V. Di Palma, M. F. Bevilacqua, A. Di Matteo, and L. De Stefano, “Photolithographic approaches to polymeric microneedles array fabrication for biomedical applications,” Materials (Basel) 8(12), 8661–8673 (2015).
[Crossref]

2014 (2)

E. Larrañeta, J. Moore, E. M. Vicente-Pérez, P. González-Vázquez, R. Lutton, A. D. Woolfson, and R. F. Donnelly, “A proposed model membrane and test method for microneedle insertion studies,” Int. J. Pharm. 472(1-2), 65–73 (2014).
[Crossref] [PubMed]

R. Vecchione, S. Coppola, E. Esposito, C. Casale, V. Vespini, S. Grilli, P. Ferraro, and P. A. Netti, “Electro-Drawn Drug-Loaded Biodegradable Polymer Microneedles as a Viable Route to Hypodermic Injection,” Adv. Funct. Mater. 24(23), 3515–3523 (2014).
[Crossref]

2013 (2)

H. Li, Y. Yu, S. Faraji Dana, B. Li, C.-Y. Lee, and L. Kang, “Novel engineered systems for oral, mucosal and transdermal drug delivery,” J. Drug Target. 21(7), 611–629 (2013).
[Crossref] [PubMed]

J. S. Kochhar, W. X. S. Lim, S. Zou, W. Y. Foo, J. Pan, and L. Kang, “Microneedle Integrated Transdermal Patch for Fast Onset and Sustained Delivery of Lidocaine,” Mol. Pharm. 10(11), 4272–4280 (2013).
[Crossref] [PubMed]

2012 (3)

R. F. Donnelly, T. R. R. Singh, M. J. Garland, K. Migalska, R. Majithiya, C. M. McCrudden, P. L. Kole, T. M. T. Mahmood, H. O. McCarthy, and A. D. Woolfson, “Hydrogel-forming microneedle arrays for enhanced transdermal drug delivery,” Adv. Funct. Mater. 22(23), 4879–4890 (2012).
[Crossref] [PubMed]

G. Valdés-Ramírez, J. R. Windmiller, J. C. Claussen, A. G. Martinez, F. Kuralay, M. Zhou, N. Zhou, R. Polsky, P. R. Miller, R. Narayan, and J. Wang, “Multiplexed and switchable release of distinct fluids from microneedle platforms via conducting polymer nanoactuators for potential drug delivery,” Sens. Actuators B Chem. 161(1), 1018–1024 (2012).
[Crossref] [PubMed]

P. R. Miller, S. A. Skoog, T. L. Edwards, D. M. Lopez, D. R. Wheeler, D. C. Arango, X. Xiao, S. M. Brozik, J. Wang, R. Polsky, and R. J. Narayan, “Multiplexed Microneedle-based Biosensor Array for Characterization of Metabolic Acidosis,” Talanta 88, 739–742 (2012).
[Crossref] [PubMed]

2011 (1)

M. W. Ashraf, S. Tayyaba, and N. Afzulpurkar, “Micro Electromechanical Systems (MEMS) Based Microfluidic Devices for Biomedical Applications,” Int. J. Mol. Sci. 12(6), 3648–3704 (2011).
[Crossref] [PubMed]

2010 (1)

R. F. Donnelly, T. R. Raj Singh, and A. D. Woolfson, “Microneedle-based drug delivery systems: Microfabrication, drug delivery, and safety,” Drug Deliv. 17(4), 187–207 (2010).
[Crossref] [PubMed]

2008 (2)

L. De Stefano, I. Rea, P. Giardina, A. Armenante, and I. Rendina, “Protein modified porous silicon nanostructures,” Adv. Mater. 20(8), 1529–1533 (2008).
[Crossref]

M. R. Prausnitz and R. Langer, “Transdermal drug delivery,” Nat. Biotechnol. 26(11), 1261–1268 (2008).
[Crossref] [PubMed]

2007 (1)

I. Rendina, I. Rea, L. Rotiroti, and L. De Stefano, “Porous Silicon Based Optical Biosensors and Biochips,” Physica E 38(1-2), 188–192 (2007).
[Crossref]

2006 (1)

L. De Stefano, M. Rossi, M. Staiano, G. Mamone, A. Parracino, L. Rotiroti, I. Rendina, M. Rossi, and S. D’Auria, “Glutamine-binding protein from Escherichia coli specifically binds a wheat gliadin peptide allowing the design of a new porous silicon-based optical biosensor,” J. Proteome Res. 5(5), 1241–1245 (2006).
[Crossref] [PubMed]

2005 (1)

N. Wilke, A. Mulcahy, S.-R. Ye, and A. Morrissey, “Process optimization and characterization of silicon microneedles fabricated by wet etch technology,” Microelectronics J. 36(7), 650–656 (2005).
[Crossref]

2004 (3)

F. Chabri, K. Bouris, T. Jones, D. Barrow, A. Hann, C. Allender, K. Brain, and J. Birchall, “Microfabricated silicon microneedles for nonviral cutaneous gene delivery,” Br. J. Dermatol. 150(5), 869–877 (2004).
[Crossref] [PubMed]

E. V. Mukerjee, S. D. Collins, R. R. Isseroff, and R. L. Smith, “Microneedle array for transdermal biological fluid extraction and in situ analysis,” Sens. Actuators A Phys. 114(2-3), 267–275 (2004).
[Crossref]

L. De Stefano, L. Moretti, I. Rendina, and A. M. Rossi, “Time-resolved sensing of chemical species in porous silicon optical microcavity,” Sens. Actuators B Chem. 100(1-2), 168–172 (2004).
[Crossref]

2003 (1)

J. L. Tan, J. Tien, D. M. Pirone, D. S. Gray, K. Bhadriraju, and C. S. Chen, “Cells lying on a bed of microneedles: An approach to isolate mechanical force,” Proc. Natl. Acad. Sci. U.S.A. 100(4), 1484–1489 (2003).
[Crossref] [PubMed]

2001 (2)

M. B. Mellott, K. Searcy, and M. V. Pishko, “Release of protein from highly cross-linked hydrogels of poly(ethylene glycol) diacrylate fabricated by UV polymerization,” Biomaterials 22(9), 929–941 (2001).
[Crossref] [PubMed]

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(2), 502–504 (2001).
[Crossref] [PubMed]

1998 (1)

S. Henry, D. V. McAllister, M. G. Allen, and M. R. Prausnitz, “Microfabricated Microneedles: A Novel Approach to Transdermal Drug Delivery,” J. Pharm. Sci. 87(8), 922–925 (1998).
[Crossref] [PubMed]

1997 (1)

M. R. Prausnitz, “Reversible skin permeabilization for transdermal delivery of macromolecules,” Crit. Rev. Ther. Drug Carrier Syst. 14(4), 455–483 (1997).
[Crossref] [PubMed]

Afzulpurkar, N.

M. W. Ashraf, S. Tayyaba, and N. Afzulpurkar, “Micro Electromechanical Systems (MEMS) Based Microfluidic Devices for Biomedical Applications,” Int. J. Mol. Sci. 12(6), 3648–3704 (2011).
[Crossref] [PubMed]

Allen, M. G.

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(2), 502–504 (2001).
[Crossref] [PubMed]

S. Henry, D. V. McAllister, M. G. Allen, and M. R. Prausnitz, “Microfabricated Microneedles: A Novel Approach to Transdermal Drug Delivery,” J. Pharm. Sci. 87(8), 922–925 (1998).
[Crossref] [PubMed]

Allender, C.

F. Chabri, K. Bouris, T. Jones, D. Barrow, A. Hann, C. Allender, K. Brain, and J. Birchall, “Microfabricated silicon microneedles for nonviral cutaneous gene delivery,” Br. J. Dermatol. 150(5), 869–877 (2004).
[Crossref] [PubMed]

Anderson, S. I.

J. R. Henstock, L. T. Canham, and S. I. Anderson, “Silicon: The evolution of its use in biomaterials,” Acta Biomater. 11, 17–26 (2015).
[Crossref] [PubMed]

Arango, D. C.

P. R. Miller, S. A. Skoog, T. L. Edwards, D. M. Lopez, D. R. Wheeler, D. C. Arango, X. Xiao, S. M. Brozik, J. Wang, R. Polsky, and R. J. Narayan, “Multiplexed Microneedle-based Biosensor Array for Characterization of Metabolic Acidosis,” Talanta 88, 739–742 (2012).
[Crossref] [PubMed]

Armenante, A.

L. De Stefano, I. Rea, P. Giardina, A. Armenante, and I. Rendina, “Protein modified porous silicon nanostructures,” Adv. Mater. 20(8), 1529–1533 (2008).
[Crossref]

Ashraf, M. W.

M. W. Ashraf, S. Tayyaba, and N. Afzulpurkar, “Micro Electromechanical Systems (MEMS) Based Microfluidic Devices for Biomedical Applications,” Int. J. Mol. Sci. 12(6), 3648–3704 (2011).
[Crossref] [PubMed]

Barillaro, G.

L. Ventrelli, L. Marsilio Strambini, and G. Barillaro, “Microneedles for Transdermal Biosensing: Current Picture and Future Direction,” Adv. Healthc. Mater. 4(17), 2606–2640 (2015).
[Crossref] [PubMed]

Barrow, D.

F. Chabri, K. Bouris, T. Jones, D. Barrow, A. Hann, C. Allender, K. Brain, and J. Birchall, “Microfabricated silicon microneedles for nonviral cutaneous gene delivery,” Br. J. Dermatol. 150(5), 869–877 (2004).
[Crossref] [PubMed]

Bevilacqua, M. F.

P. Dardano, A. Caliò, V. Di Palma, M. F. Bevilacqua, A. Di Matteo, and L. De Stefano, “Photolithographic approaches to polymeric microneedles array fabrication for biomedical applications,” Materials (Basel) 8(12), 8661–8673 (2015).
[Crossref]

Bhadriraju, K.

J. L. Tan, J. Tien, D. M. Pirone, D. S. Gray, K. Bhadriraju, and C. S. Chen, “Cells lying on a bed of microneedles: An approach to isolate mechanical force,” Proc. Natl. Acad. Sci. U.S.A. 100(4), 1484–1489 (2003).
[Crossref] [PubMed]

Birchall, J.

F. Chabri, K. Bouris, T. Jones, D. Barrow, A. Hann, C. Allender, K. Brain, and J. Birchall, “Microfabricated silicon microneedles for nonviral cutaneous gene delivery,” Br. J. Dermatol. 150(5), 869–877 (2004).
[Crossref] [PubMed]

Bouris, K.

F. Chabri, K. Bouris, T. Jones, D. Barrow, A. Hann, C. Allender, K. Brain, and J. Birchall, “Microfabricated silicon microneedles for nonviral cutaneous gene delivery,” Br. J. Dermatol. 150(5), 869–877 (2004).
[Crossref] [PubMed]

Brain, K.

F. Chabri, K. Bouris, T. Jones, D. Barrow, A. Hann, C. Allender, K. Brain, and J. Birchall, “Microfabricated silicon microneedles for nonviral cutaneous gene delivery,” Br. J. Dermatol. 150(5), 869–877 (2004).
[Crossref] [PubMed]

Brozik, S. M.

P. R. Miller, S. A. Skoog, T. L. Edwards, D. M. Lopez, D. R. Wheeler, D. C. Arango, X. Xiao, S. M. Brozik, J. Wang, R. Polsky, and R. J. Narayan, “Multiplexed Microneedle-based Biosensor Array for Characterization of Metabolic Acidosis,” Talanta 88, 739–742 (2012).
[Crossref] [PubMed]

Cahill, E. M.

E. M. Cahill and E. D. O’Cearbhaill, “Toward Biofunctional Microneedles for Stimulus Responsive Drug Delivery,” Bioconjug. Chem. 26(7), 1289–1296 (2015).
[Crossref] [PubMed]

Caliò, A.

P. Dardano, A. Caliò, V. Di Palma, M. F. Bevilacqua, A. Di Matteo, and L. De Stefano, “Photolithographic approaches to polymeric microneedles array fabrication for biomedical applications,” Materials (Basel) 8(12), 8661–8673 (2015).
[Crossref]

Canham, L. T.

J. R. Henstock, L. T. Canham, and S. I. Anderson, “Silicon: The evolution of its use in biomaterials,” Acta Biomater. 11, 17–26 (2015).
[Crossref] [PubMed]

Casale, C.

R. Vecchione, S. Coppola, E. Esposito, C. Casale, V. Vespini, S. Grilli, P. Ferraro, and P. A. Netti, “Electro-Drawn Drug-Loaded Biodegradable Polymer Microneedles as a Viable Route to Hypodermic Injection,” Adv. Funct. Mater. 24(23), 3515–3523 (2014).
[Crossref]

Chabri, F.

F. Chabri, K. Bouris, T. Jones, D. Barrow, A. Hann, C. Allender, K. Brain, and J. Birchall, “Microfabricated silicon microneedles for nonviral cutaneous gene delivery,” Br. J. Dermatol. 150(5), 869–877 (2004).
[Crossref] [PubMed]

Chen, C. S.

J. L. Tan, J. Tien, D. M. Pirone, D. S. Gray, K. Bhadriraju, and C. S. Chen, “Cells lying on a bed of microneedles: An approach to isolate mechanical force,” Proc. Natl. Acad. Sci. U.S.A. 100(4), 1484–1489 (2003).
[Crossref] [PubMed]

Claussen, J. C.

G. Valdés-Ramírez, J. R. Windmiller, J. C. Claussen, A. G. Martinez, F. Kuralay, M. Zhou, N. Zhou, R. Polsky, P. R. Miller, R. Narayan, and J. Wang, “Multiplexed and switchable release of distinct fluids from microneedle platforms via conducting polymer nanoactuators for potential drug delivery,” Sens. Actuators B Chem. 161(1), 1018–1024 (2012).
[Crossref] [PubMed]

Collins, S. D.

E. V. Mukerjee, S. D. Collins, R. R. Isseroff, and R. L. Smith, “Microneedle array for transdermal biological fluid extraction and in situ analysis,” Sens. Actuators A Phys. 114(2-3), 267–275 (2004).
[Crossref]

Coppola, S.

R. Vecchione, S. Coppola, E. Esposito, C. Casale, V. Vespini, S. Grilli, P. Ferraro, and P. A. Netti, “Electro-Drawn Drug-Loaded Biodegradable Polymer Microneedles as a Viable Route to Hypodermic Injection,” Adv. Funct. Mater. 24(23), 3515–3523 (2014).
[Crossref]

D’Auria, S.

L. De Stefano, M. Rossi, M. Staiano, G. Mamone, A. Parracino, L. Rotiroti, I. Rendina, M. Rossi, and S. D’Auria, “Glutamine-binding protein from Escherichia coli specifically binds a wheat gliadin peptide allowing the design of a new porous silicon-based optical biosensor,” J. Proteome Res. 5(5), 1241–1245 (2006).
[Crossref] [PubMed]

Dardano, P.

P. Dardano, A. Caliò, V. Di Palma, M. F. Bevilacqua, A. Di Matteo, and L. De Stefano, “Photolithographic approaches to polymeric microneedles array fabrication for biomedical applications,” Materials (Basel) 8(12), 8661–8673 (2015).
[Crossref]

De Stefano, L.

P. Dardano, A. Caliò, V. Di Palma, M. F. Bevilacqua, A. Di Matteo, and L. De Stefano, “Photolithographic approaches to polymeric microneedles array fabrication for biomedical applications,” Materials (Basel) 8(12), 8661–8673 (2015).
[Crossref]

L. De Stefano, I. Rea, P. Giardina, A. Armenante, and I. Rendina, “Protein modified porous silicon nanostructures,” Adv. Mater. 20(8), 1529–1533 (2008).
[Crossref]

I. Rendina, I. Rea, L. Rotiroti, and L. De Stefano, “Porous Silicon Based Optical Biosensors and Biochips,” Physica E 38(1-2), 188–192 (2007).
[Crossref]

L. De Stefano, M. Rossi, M. Staiano, G. Mamone, A. Parracino, L. Rotiroti, I. Rendina, M. Rossi, and S. D’Auria, “Glutamine-binding protein from Escherichia coli specifically binds a wheat gliadin peptide allowing the design of a new porous silicon-based optical biosensor,” J. Proteome Res. 5(5), 1241–1245 (2006).
[Crossref] [PubMed]

L. De Stefano, L. Moretti, I. Rendina, and A. M. Rossi, “Time-resolved sensing of chemical species in porous silicon optical microcavity,” Sens. Actuators B Chem. 100(1-2), 168–172 (2004).
[Crossref]

Denson, D. D.

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(2), 502–504 (2001).
[Crossref] [PubMed]

Di Matteo, A.

P. Dardano, A. Caliò, V. Di Palma, M. F. Bevilacqua, A. Di Matteo, and L. De Stefano, “Photolithographic approaches to polymeric microneedles array fabrication for biomedical applications,” Materials (Basel) 8(12), 8661–8673 (2015).
[Crossref]

Di Palma, V.

P. Dardano, A. Caliò, V. Di Palma, M. F. Bevilacqua, A. Di Matteo, and L. De Stefano, “Photolithographic approaches to polymeric microneedles array fabrication for biomedical applications,” Materials (Basel) 8(12), 8661–8673 (2015).
[Crossref]

Donnelly, R. F.

E. Larrañeta, J. Moore, E. M. Vicente-Pérez, P. González-Vázquez, R. Lutton, A. D. Woolfson, and R. F. Donnelly, “A proposed model membrane and test method for microneedle insertion studies,” Int. J. Pharm. 472(1-2), 65–73 (2014).
[Crossref] [PubMed]

R. F. Donnelly, T. R. R. Singh, M. J. Garland, K. Migalska, R. Majithiya, C. M. McCrudden, P. L. Kole, T. M. T. Mahmood, H. O. McCarthy, and A. D. Woolfson, “Hydrogel-forming microneedle arrays for enhanced transdermal drug delivery,” Adv. Funct. Mater. 22(23), 4879–4890 (2012).
[Crossref] [PubMed]

R. F. Donnelly, T. R. Raj Singh, and A. D. Woolfson, “Microneedle-based drug delivery systems: Microfabrication, drug delivery, and safety,” Drug Deliv. 17(4), 187–207 (2010).
[Crossref] [PubMed]

Edwards, T. L.

P. R. Miller, S. A. Skoog, T. L. Edwards, D. M. Lopez, D. R. Wheeler, D. C. Arango, X. Xiao, S. M. Brozik, J. Wang, R. Polsky, and R. J. Narayan, “Multiplexed Microneedle-based Biosensor Array for Characterization of Metabolic Acidosis,” Talanta 88, 739–742 (2012).
[Crossref] [PubMed]

Esposito, E.

R. Vecchione, S. Coppola, E. Esposito, C. Casale, V. Vespini, S. Grilli, P. Ferraro, and P. A. Netti, “Electro-Drawn Drug-Loaded Biodegradable Polymer Microneedles as a Viable Route to Hypodermic Injection,” Adv. Funct. Mater. 24(23), 3515–3523 (2014).
[Crossref]

Faraji Dana, S.

H. Li, Y. Yu, S. Faraji Dana, B. Li, C.-Y. Lee, and L. Kang, “Novel engineered systems for oral, mucosal and transdermal drug delivery,” J. Drug Target. 21(7), 611–629 (2013).
[Crossref] [PubMed]

Ferraro, P.

R. Vecchione, S. Coppola, E. Esposito, C. Casale, V. Vespini, S. Grilli, P. Ferraro, and P. A. Netti, “Electro-Drawn Drug-Loaded Biodegradable Polymer Microneedles as a Viable Route to Hypodermic Injection,” Adv. Funct. Mater. 24(23), 3515–3523 (2014).
[Crossref]

Foo, W. Y.

J. S. Kochhar, W. X. S. Lim, S. Zou, W. Y. Foo, J. Pan, and L. Kang, “Microneedle Integrated Transdermal Patch for Fast Onset and Sustained Delivery of Lidocaine,” Mol. Pharm. 10(11), 4272–4280 (2013).
[Crossref] [PubMed]

Garland, M. J.

R. F. Donnelly, T. R. R. Singh, M. J. Garland, K. Migalska, R. Majithiya, C. M. McCrudden, P. L. Kole, T. M. T. Mahmood, H. O. McCarthy, and A. D. Woolfson, “Hydrogel-forming microneedle arrays for enhanced transdermal drug delivery,” Adv. Funct. Mater. 22(23), 4879–4890 (2012).
[Crossref] [PubMed]

Giardina, P.

L. De Stefano, I. Rea, P. Giardina, A. Armenante, and I. Rendina, “Protein modified porous silicon nanostructures,” Adv. Mater. 20(8), 1529–1533 (2008).
[Crossref]

González-Vázquez, P.

E. Larrañeta, J. Moore, E. M. Vicente-Pérez, P. González-Vázquez, R. Lutton, A. D. Woolfson, and R. F. Donnelly, “A proposed model membrane and test method for microneedle insertion studies,” Int. J. Pharm. 472(1-2), 65–73 (2014).
[Crossref] [PubMed]

Gray, D. S.

J. L. Tan, J. Tien, D. M. Pirone, D. S. Gray, K. Bhadriraju, and C. S. Chen, “Cells lying on a bed of microneedles: An approach to isolate mechanical force,” Proc. Natl. Acad. Sci. U.S.A. 100(4), 1484–1489 (2003).
[Crossref] [PubMed]

Grilli, S.

R. Vecchione, S. Coppola, E. Esposito, C. Casale, V. Vespini, S. Grilli, P. Ferraro, and P. A. Netti, “Electro-Drawn Drug-Loaded Biodegradable Polymer Microneedles as a Viable Route to Hypodermic Injection,” Adv. Funct. Mater. 24(23), 3515–3523 (2014).
[Crossref]

Hann, A.

F. Chabri, K. Bouris, T. Jones, D. Barrow, A. Hann, C. Allender, K. Brain, and J. Birchall, “Microfabricated silicon microneedles for nonviral cutaneous gene delivery,” Br. J. Dermatol. 150(5), 869–877 (2004).
[Crossref] [PubMed]

Henry, S.

S. Henry, D. V. McAllister, M. G. Allen, and M. R. Prausnitz, “Microfabricated Microneedles: A Novel Approach to Transdermal Drug Delivery,” J. Pharm. Sci. 87(8), 922–925 (1998).
[Crossref] [PubMed]

Henstock, J. R.

J. R. Henstock, L. T. Canham, and S. I. Anderson, “Silicon: The evolution of its use in biomaterials,” Acta Biomater. 11, 17–26 (2015).
[Crossref] [PubMed]

Hord, A. H.

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(2), 502–504 (2001).
[Crossref] [PubMed]

Isseroff, R. R.

E. V. Mukerjee, S. D. Collins, R. R. Isseroff, and R. L. Smith, “Microneedle array for transdermal biological fluid extraction and in situ analysis,” Sens. Actuators A Phys. 114(2-3), 267–275 (2004).
[Crossref]

Jones, T.

F. Chabri, K. Bouris, T. Jones, D. Barrow, A. Hann, C. Allender, K. Brain, and J. Birchall, “Microfabricated silicon microneedles for nonviral cutaneous gene delivery,” Br. J. Dermatol. 150(5), 869–877 (2004).
[Crossref] [PubMed]

Kang, L.

J. S. Kochhar, W. X. S. Lim, S. Zou, W. Y. Foo, J. Pan, and L. Kang, “Microneedle Integrated Transdermal Patch for Fast Onset and Sustained Delivery of Lidocaine,” Mol. Pharm. 10(11), 4272–4280 (2013).
[Crossref] [PubMed]

H. Li, Y. Yu, S. Faraji Dana, B. Li, C.-Y. Lee, and L. Kang, “Novel engineered systems for oral, mucosal and transdermal drug delivery,” J. Drug Target. 21(7), 611–629 (2013).
[Crossref] [PubMed]

Kaushik, S.

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(2), 502–504 (2001).
[Crossref] [PubMed]

Kochhar, J. S.

J. S. Kochhar, W. X. S. Lim, S. Zou, W. Y. Foo, J. Pan, and L. Kang, “Microneedle Integrated Transdermal Patch for Fast Onset and Sustained Delivery of Lidocaine,” Mol. Pharm. 10(11), 4272–4280 (2013).
[Crossref] [PubMed]

Kole, P. L.

R. F. Donnelly, T. R. R. Singh, M. J. Garland, K. Migalska, R. Majithiya, C. M. McCrudden, P. L. Kole, T. M. T. Mahmood, H. O. McCarthy, and A. D. Woolfson, “Hydrogel-forming microneedle arrays for enhanced transdermal drug delivery,” Adv. Funct. Mater. 22(23), 4879–4890 (2012).
[Crossref] [PubMed]

Kuralay, F.

G. Valdés-Ramírez, J. R. Windmiller, J. C. Claussen, A. G. Martinez, F. Kuralay, M. Zhou, N. Zhou, R. Polsky, P. R. Miller, R. Narayan, and J. Wang, “Multiplexed and switchable release of distinct fluids from microneedle platforms via conducting polymer nanoactuators for potential drug delivery,” Sens. Actuators B Chem. 161(1), 1018–1024 (2012).
[Crossref] [PubMed]

Langer, R.

M. R. Prausnitz and R. Langer, “Transdermal drug delivery,” Nat. Biotechnol. 26(11), 1261–1268 (2008).
[Crossref] [PubMed]

Larrañeta, E.

E. Larrañeta, J. Moore, E. M. Vicente-Pérez, P. González-Vázquez, R. Lutton, A. D. Woolfson, and R. F. Donnelly, “A proposed model membrane and test method for microneedle insertion studies,” Int. J. Pharm. 472(1-2), 65–73 (2014).
[Crossref] [PubMed]

Lee, C.-Y.

H. Li, Y. Yu, S. Faraji Dana, B. Li, C.-Y. Lee, and L. Kang, “Novel engineered systems for oral, mucosal and transdermal drug delivery,” J. Drug Target. 21(7), 611–629 (2013).
[Crossref] [PubMed]

Li, B.

H. Li, Y. Yu, S. Faraji Dana, B. Li, C.-Y. Lee, and L. Kang, “Novel engineered systems for oral, mucosal and transdermal drug delivery,” J. Drug Target. 21(7), 611–629 (2013).
[Crossref] [PubMed]

Li, H.

H. Li, Y. Yu, S. Faraji Dana, B. Li, C.-Y. Lee, and L. Kang, “Novel engineered systems for oral, mucosal and transdermal drug delivery,” J. Drug Target. 21(7), 611–629 (2013).
[Crossref] [PubMed]

Lim, W. X. S.

J. S. Kochhar, W. X. S. Lim, S. Zou, W. Y. Foo, J. Pan, and L. Kang, “Microneedle Integrated Transdermal Patch for Fast Onset and Sustained Delivery of Lidocaine,” Mol. Pharm. 10(11), 4272–4280 (2013).
[Crossref] [PubMed]

Lopez, D. M.

P. R. Miller, S. A. Skoog, T. L. Edwards, D. M. Lopez, D. R. Wheeler, D. C. Arango, X. Xiao, S. M. Brozik, J. Wang, R. Polsky, and R. J. Narayan, “Multiplexed Microneedle-based Biosensor Array for Characterization of Metabolic Acidosis,” Talanta 88, 739–742 (2012).
[Crossref] [PubMed]

Lutton, R.

E. Larrañeta, J. Moore, E. M. Vicente-Pérez, P. González-Vázquez, R. Lutton, A. D. Woolfson, and R. F. Donnelly, “A proposed model membrane and test method for microneedle insertion studies,” Int. J. Pharm. 472(1-2), 65–73 (2014).
[Crossref] [PubMed]

Mahmood, T. M. T.

R. F. Donnelly, T. R. R. Singh, M. J. Garland, K. Migalska, R. Majithiya, C. M. McCrudden, P. L. Kole, T. M. T. Mahmood, H. O. McCarthy, and A. D. Woolfson, “Hydrogel-forming microneedle arrays for enhanced transdermal drug delivery,” Adv. Funct. Mater. 22(23), 4879–4890 (2012).
[Crossref] [PubMed]

Majithiya, R.

R. F. Donnelly, T. R. R. Singh, M. J. Garland, K. Migalska, R. Majithiya, C. M. McCrudden, P. L. Kole, T. M. T. Mahmood, H. O. McCarthy, and A. D. Woolfson, “Hydrogel-forming microneedle arrays for enhanced transdermal drug delivery,” Adv. Funct. Mater. 22(23), 4879–4890 (2012).
[Crossref] [PubMed]

Mamone, G.

L. De Stefano, M. Rossi, M. Staiano, G. Mamone, A. Parracino, L. Rotiroti, I. Rendina, M. Rossi, and S. D’Auria, “Glutamine-binding protein from Escherichia coli specifically binds a wheat gliadin peptide allowing the design of a new porous silicon-based optical biosensor,” J. Proteome Res. 5(5), 1241–1245 (2006).
[Crossref] [PubMed]

Marsilio Strambini, L.

L. Ventrelli, L. Marsilio Strambini, and G. Barillaro, “Microneedles for Transdermal Biosensing: Current Picture and Future Direction,” Adv. Healthc. Mater. 4(17), 2606–2640 (2015).
[Crossref] [PubMed]

Martinez, A. G.

G. Valdés-Ramírez, J. R. Windmiller, J. C. Claussen, A. G. Martinez, F. Kuralay, M. Zhou, N. Zhou, R. Polsky, P. R. Miller, R. Narayan, and J. Wang, “Multiplexed and switchable release of distinct fluids from microneedle platforms via conducting polymer nanoactuators for potential drug delivery,” Sens. Actuators B Chem. 161(1), 1018–1024 (2012).
[Crossref] [PubMed]

McAllister, D. V.

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(2), 502–504 (2001).
[Crossref] [PubMed]

S. Henry, D. V. McAllister, M. G. Allen, and M. R. Prausnitz, “Microfabricated Microneedles: A Novel Approach to Transdermal Drug Delivery,” J. Pharm. Sci. 87(8), 922–925 (1998).
[Crossref] [PubMed]

McCarthy, H. O.

R. F. Donnelly, T. R. R. Singh, M. J. Garland, K. Migalska, R. Majithiya, C. M. McCrudden, P. L. Kole, T. M. T. Mahmood, H. O. McCarthy, and A. D. Woolfson, “Hydrogel-forming microneedle arrays for enhanced transdermal drug delivery,” Adv. Funct. Mater. 22(23), 4879–4890 (2012).
[Crossref] [PubMed]

McCrudden, C. M.

R. F. Donnelly, T. R. R. Singh, M. J. Garland, K. Migalska, R. Majithiya, C. M. McCrudden, P. L. Kole, T. M. T. Mahmood, H. O. McCarthy, and A. D. Woolfson, “Hydrogel-forming microneedle arrays for enhanced transdermal drug delivery,” Adv. Funct. Mater. 22(23), 4879–4890 (2012).
[Crossref] [PubMed]

Mellott, M. B.

M. B. Mellott, K. Searcy, and M. V. Pishko, “Release of protein from highly cross-linked hydrogels of poly(ethylene glycol) diacrylate fabricated by UV polymerization,” Biomaterials 22(9), 929–941 (2001).
[Crossref] [PubMed]

Migalska, K.

R. F. Donnelly, T. R. R. Singh, M. J. Garland, K. Migalska, R. Majithiya, C. M. McCrudden, P. L. Kole, T. M. T. Mahmood, H. O. McCarthy, and A. D. Woolfson, “Hydrogel-forming microneedle arrays for enhanced transdermal drug delivery,” Adv. Funct. Mater. 22(23), 4879–4890 (2012).
[Crossref] [PubMed]

Miller, P. R.

G. Valdés-Ramírez, J. R. Windmiller, J. C. Claussen, A. G. Martinez, F. Kuralay, M. Zhou, N. Zhou, R. Polsky, P. R. Miller, R. Narayan, and J. Wang, “Multiplexed and switchable release of distinct fluids from microneedle platforms via conducting polymer nanoactuators for potential drug delivery,” Sens. Actuators B Chem. 161(1), 1018–1024 (2012).
[Crossref] [PubMed]

P. R. Miller, S. A. Skoog, T. L. Edwards, D. M. Lopez, D. R. Wheeler, D. C. Arango, X. Xiao, S. M. Brozik, J. Wang, R. Polsky, and R. J. Narayan, “Multiplexed Microneedle-based Biosensor Array for Characterization of Metabolic Acidosis,” Talanta 88, 739–742 (2012).
[Crossref] [PubMed]

Moore, J.

E. Larrañeta, J. Moore, E. M. Vicente-Pérez, P. González-Vázquez, R. Lutton, A. D. Woolfson, and R. F. Donnelly, “A proposed model membrane and test method for microneedle insertion studies,” Int. J. Pharm. 472(1-2), 65–73 (2014).
[Crossref] [PubMed]

Moretti, L.

L. De Stefano, L. Moretti, I. Rendina, and A. M. Rossi, “Time-resolved sensing of chemical species in porous silicon optical microcavity,” Sens. Actuators B Chem. 100(1-2), 168–172 (2004).
[Crossref]

Morrissey, A.

N. Wilke, A. Mulcahy, S.-R. Ye, and A. Morrissey, “Process optimization and characterization of silicon microneedles fabricated by wet etch technology,” Microelectronics J. 36(7), 650–656 (2005).
[Crossref]

Mukerjee, E. V.

E. V. Mukerjee, S. D. Collins, R. R. Isseroff, and R. L. Smith, “Microneedle array for transdermal biological fluid extraction and in situ analysis,” Sens. Actuators A Phys. 114(2-3), 267–275 (2004).
[Crossref]

Mulcahy, A.

N. Wilke, A. Mulcahy, S.-R. Ye, and A. Morrissey, “Process optimization and characterization of silicon microneedles fabricated by wet etch technology,” Microelectronics J. 36(7), 650–656 (2005).
[Crossref]

Narayan, R.

G. Valdés-Ramírez, J. R. Windmiller, J. C. Claussen, A. G. Martinez, F. Kuralay, M. Zhou, N. Zhou, R. Polsky, P. R. Miller, R. Narayan, and J. Wang, “Multiplexed and switchable release of distinct fluids from microneedle platforms via conducting polymer nanoactuators for potential drug delivery,” Sens. Actuators B Chem. 161(1), 1018–1024 (2012).
[Crossref] [PubMed]

Narayan, R. J.

P. R. Miller, S. A. Skoog, T. L. Edwards, D. M. Lopez, D. R. Wheeler, D. C. Arango, X. Xiao, S. M. Brozik, J. Wang, R. Polsky, and R. J. Narayan, “Multiplexed Microneedle-based Biosensor Array for Characterization of Metabolic Acidosis,” Talanta 88, 739–742 (2012).
[Crossref] [PubMed]

Netti, P. A.

R. Vecchione, S. Coppola, E. Esposito, C. Casale, V. Vespini, S. Grilli, P. Ferraro, and P. A. Netti, “Electro-Drawn Drug-Loaded Biodegradable Polymer Microneedles as a Viable Route to Hypodermic Injection,” Adv. Funct. Mater. 24(23), 3515–3523 (2014).
[Crossref]

O’Cearbhaill, E. D.

E. M. Cahill and E. D. O’Cearbhaill, “Toward Biofunctional Microneedles for Stimulus Responsive Drug Delivery,” Bioconjug. Chem. 26(7), 1289–1296 (2015).
[Crossref] [PubMed]

Pan, J.

J. S. Kochhar, W. X. S. Lim, S. Zou, W. Y. Foo, J. Pan, and L. Kang, “Microneedle Integrated Transdermal Patch for Fast Onset and Sustained Delivery of Lidocaine,” Mol. Pharm. 10(11), 4272–4280 (2013).
[Crossref] [PubMed]

Parracino, A.

L. De Stefano, M. Rossi, M. Staiano, G. Mamone, A. Parracino, L. Rotiroti, I. Rendina, M. Rossi, and S. D’Auria, “Glutamine-binding protein from Escherichia coli specifically binds a wheat gliadin peptide allowing the design of a new porous silicon-based optical biosensor,” J. Proteome Res. 5(5), 1241–1245 (2006).
[Crossref] [PubMed]

Pirone, D. M.

J. L. Tan, J. Tien, D. M. Pirone, D. S. Gray, K. Bhadriraju, and C. S. Chen, “Cells lying on a bed of microneedles: An approach to isolate mechanical force,” Proc. Natl. Acad. Sci. U.S.A. 100(4), 1484–1489 (2003).
[Crossref] [PubMed]

Pishko, M. V.

M. B. Mellott, K. Searcy, and M. V. Pishko, “Release of protein from highly cross-linked hydrogels of poly(ethylene glycol) diacrylate fabricated by UV polymerization,” Biomaterials 22(9), 929–941 (2001).
[Crossref] [PubMed]

Polsky, R.

G. Valdés-Ramírez, J. R. Windmiller, J. C. Claussen, A. G. Martinez, F. Kuralay, M. Zhou, N. Zhou, R. Polsky, P. R. Miller, R. Narayan, and J. Wang, “Multiplexed and switchable release of distinct fluids from microneedle platforms via conducting polymer nanoactuators for potential drug delivery,” Sens. Actuators B Chem. 161(1), 1018–1024 (2012).
[Crossref] [PubMed]

P. R. Miller, S. A. Skoog, T. L. Edwards, D. M. Lopez, D. R. Wheeler, D. C. Arango, X. Xiao, S. M. Brozik, J. Wang, R. Polsky, and R. J. Narayan, “Multiplexed Microneedle-based Biosensor Array for Characterization of Metabolic Acidosis,” Talanta 88, 739–742 (2012).
[Crossref] [PubMed]

Prausnitz, M. R.

M. R. Prausnitz and R. Langer, “Transdermal drug delivery,” Nat. Biotechnol. 26(11), 1261–1268 (2008).
[Crossref] [PubMed]

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(2), 502–504 (2001).
[Crossref] [PubMed]

S. Henry, D. V. McAllister, M. G. Allen, and M. R. Prausnitz, “Microfabricated Microneedles: A Novel Approach to Transdermal Drug Delivery,” J. Pharm. Sci. 87(8), 922–925 (1998).
[Crossref] [PubMed]

M. R. Prausnitz, “Reversible skin permeabilization for transdermal delivery of macromolecules,” Crit. Rev. Ther. Drug Carrier Syst. 14(4), 455–483 (1997).
[Crossref] [PubMed]

Raj Singh, T. R.

R. F. Donnelly, T. R. Raj Singh, and A. D. Woolfson, “Microneedle-based drug delivery systems: Microfabrication, drug delivery, and safety,” Drug Deliv. 17(4), 187–207 (2010).
[Crossref] [PubMed]

Rea, I.

L. De Stefano, I. Rea, P. Giardina, A. Armenante, and I. Rendina, “Protein modified porous silicon nanostructures,” Adv. Mater. 20(8), 1529–1533 (2008).
[Crossref]

I. Rendina, I. Rea, L. Rotiroti, and L. De Stefano, “Porous Silicon Based Optical Biosensors and Biochips,” Physica E 38(1-2), 188–192 (2007).
[Crossref]

Rendina, I.

L. De Stefano, I. Rea, P. Giardina, A. Armenante, and I. Rendina, “Protein modified porous silicon nanostructures,” Adv. Mater. 20(8), 1529–1533 (2008).
[Crossref]

I. Rendina, I. Rea, L. Rotiroti, and L. De Stefano, “Porous Silicon Based Optical Biosensors and Biochips,” Physica E 38(1-2), 188–192 (2007).
[Crossref]

L. De Stefano, M. Rossi, M. Staiano, G. Mamone, A. Parracino, L. Rotiroti, I. Rendina, M. Rossi, and S. D’Auria, “Glutamine-binding protein from Escherichia coli specifically binds a wheat gliadin peptide allowing the design of a new porous silicon-based optical biosensor,” J. Proteome Res. 5(5), 1241–1245 (2006).
[Crossref] [PubMed]

L. De Stefano, L. Moretti, I. Rendina, and A. M. Rossi, “Time-resolved sensing of chemical species in porous silicon optical microcavity,” Sens. Actuators B Chem. 100(1-2), 168–172 (2004).
[Crossref]

Rossi, A. M.

L. De Stefano, L. Moretti, I. Rendina, and A. M. Rossi, “Time-resolved sensing of chemical species in porous silicon optical microcavity,” Sens. Actuators B Chem. 100(1-2), 168–172 (2004).
[Crossref]

Rossi, M.

L. De Stefano, M. Rossi, M. Staiano, G. Mamone, A. Parracino, L. Rotiroti, I. Rendina, M. Rossi, and S. D’Auria, “Glutamine-binding protein from Escherichia coli specifically binds a wheat gliadin peptide allowing the design of a new porous silicon-based optical biosensor,” J. Proteome Res. 5(5), 1241–1245 (2006).
[Crossref] [PubMed]

L. De Stefano, M. Rossi, M. Staiano, G. Mamone, A. Parracino, L. Rotiroti, I. Rendina, M. Rossi, and S. D’Auria, “Glutamine-binding protein from Escherichia coli specifically binds a wheat gliadin peptide allowing the design of a new porous silicon-based optical biosensor,” J. Proteome Res. 5(5), 1241–1245 (2006).
[Crossref] [PubMed]

Rotiroti, L.

I. Rendina, I. Rea, L. Rotiroti, and L. De Stefano, “Porous Silicon Based Optical Biosensors and Biochips,” Physica E 38(1-2), 188–192 (2007).
[Crossref]

L. De Stefano, M. Rossi, M. Staiano, G. Mamone, A. Parracino, L. Rotiroti, I. Rendina, M. Rossi, and S. D’Auria, “Glutamine-binding protein from Escherichia coli specifically binds a wheat gliadin peptide allowing the design of a new porous silicon-based optical biosensor,” J. Proteome Res. 5(5), 1241–1245 (2006).
[Crossref] [PubMed]

Searcy, K.

M. B. Mellott, K. Searcy, and M. V. Pishko, “Release of protein from highly cross-linked hydrogels of poly(ethylene glycol) diacrylate fabricated by UV polymerization,” Biomaterials 22(9), 929–941 (2001).
[Crossref] [PubMed]

Singh, T. R. R.

R. F. Donnelly, T. R. R. Singh, M. J. Garland, K. Migalska, R. Majithiya, C. M. McCrudden, P. L. Kole, T. M. T. Mahmood, H. O. McCarthy, and A. D. Woolfson, “Hydrogel-forming microneedle arrays for enhanced transdermal drug delivery,” Adv. Funct. Mater. 22(23), 4879–4890 (2012).
[Crossref] [PubMed]

Skoog, S. A.

P. R. Miller, S. A. Skoog, T. L. Edwards, D. M. Lopez, D. R. Wheeler, D. C. Arango, X. Xiao, S. M. Brozik, J. Wang, R. Polsky, and R. J. Narayan, “Multiplexed Microneedle-based Biosensor Array for Characterization of Metabolic Acidosis,” Talanta 88, 739–742 (2012).
[Crossref] [PubMed]

Smith, R. L.

E. V. Mukerjee, S. D. Collins, R. R. Isseroff, and R. L. Smith, “Microneedle array for transdermal biological fluid extraction and in situ analysis,” Sens. Actuators A Phys. 114(2-3), 267–275 (2004).
[Crossref]

Smitra, S.

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(2), 502–504 (2001).
[Crossref] [PubMed]

Staiano, M.

L. De Stefano, M. Rossi, M. Staiano, G. Mamone, A. Parracino, L. Rotiroti, I. Rendina, M. Rossi, and S. D’Auria, “Glutamine-binding protein from Escherichia coli specifically binds a wheat gliadin peptide allowing the design of a new porous silicon-based optical biosensor,” J. Proteome Res. 5(5), 1241–1245 (2006).
[Crossref] [PubMed]

Tan, J. L.

J. L. Tan, J. Tien, D. M. Pirone, D. S. Gray, K. Bhadriraju, and C. S. Chen, “Cells lying on a bed of microneedles: An approach to isolate mechanical force,” Proc. Natl. Acad. Sci. U.S.A. 100(4), 1484–1489 (2003).
[Crossref] [PubMed]

Tayyaba, S.

M. W. Ashraf, S. Tayyaba, and N. Afzulpurkar, “Micro Electromechanical Systems (MEMS) Based Microfluidic Devices for Biomedical Applications,” Int. J. Mol. Sci. 12(6), 3648–3704 (2011).
[Crossref] [PubMed]

Tien, J.

J. L. Tan, J. Tien, D. M. Pirone, D. S. Gray, K. Bhadriraju, and C. S. Chen, “Cells lying on a bed of microneedles: An approach to isolate mechanical force,” Proc. Natl. Acad. Sci. U.S.A. 100(4), 1484–1489 (2003).
[Crossref] [PubMed]

Valdés-Ramírez, G.

G. Valdés-Ramírez, J. R. Windmiller, J. C. Claussen, A. G. Martinez, F. Kuralay, M. Zhou, N. Zhou, R. Polsky, P. R. Miller, R. Narayan, and J. Wang, “Multiplexed and switchable release of distinct fluids from microneedle platforms via conducting polymer nanoactuators for potential drug delivery,” Sens. Actuators B Chem. 161(1), 1018–1024 (2012).
[Crossref] [PubMed]

Vecchione, R.

R. Vecchione, S. Coppola, E. Esposito, C. Casale, V. Vespini, S. Grilli, P. Ferraro, and P. A. Netti, “Electro-Drawn Drug-Loaded Biodegradable Polymer Microneedles as a Viable Route to Hypodermic Injection,” Adv. Funct. Mater. 24(23), 3515–3523 (2014).
[Crossref]

Ventrelli, L.

L. Ventrelli, L. Marsilio Strambini, and G. Barillaro, “Microneedles for Transdermal Biosensing: Current Picture and Future Direction,” Adv. Healthc. Mater. 4(17), 2606–2640 (2015).
[Crossref] [PubMed]

Vespini, V.

R. Vecchione, S. Coppola, E. Esposito, C. Casale, V. Vespini, S. Grilli, P. Ferraro, and P. A. Netti, “Electro-Drawn Drug-Loaded Biodegradable Polymer Microneedles as a Viable Route to Hypodermic Injection,” Adv. Funct. Mater. 24(23), 3515–3523 (2014).
[Crossref]

Vicente-Pérez, E. M.

E. Larrañeta, J. Moore, E. M. Vicente-Pérez, P. González-Vázquez, R. Lutton, A. D. Woolfson, and R. F. Donnelly, “A proposed model membrane and test method for microneedle insertion studies,” Int. J. Pharm. 472(1-2), 65–73 (2014).
[Crossref] [PubMed]

Wang, J.

G. Valdés-Ramírez, J. R. Windmiller, J. C. Claussen, A. G. Martinez, F. Kuralay, M. Zhou, N. Zhou, R. Polsky, P. R. Miller, R. Narayan, and J. Wang, “Multiplexed and switchable release of distinct fluids from microneedle platforms via conducting polymer nanoactuators for potential drug delivery,” Sens. Actuators B Chem. 161(1), 1018–1024 (2012).
[Crossref] [PubMed]

P. R. Miller, S. A. Skoog, T. L. Edwards, D. M. Lopez, D. R. Wheeler, D. C. Arango, X. Xiao, S. M. Brozik, J. Wang, R. Polsky, and R. J. Narayan, “Multiplexed Microneedle-based Biosensor Array for Characterization of Metabolic Acidosis,” Talanta 88, 739–742 (2012).
[Crossref] [PubMed]

Wheeler, D. R.

P. R. Miller, S. A. Skoog, T. L. Edwards, D. M. Lopez, D. R. Wheeler, D. C. Arango, X. Xiao, S. M. Brozik, J. Wang, R. Polsky, and R. J. Narayan, “Multiplexed Microneedle-based Biosensor Array for Characterization of Metabolic Acidosis,” Talanta 88, 739–742 (2012).
[Crossref] [PubMed]

Wilke, N.

N. Wilke, A. Mulcahy, S.-R. Ye, and A. Morrissey, “Process optimization and characterization of silicon microneedles fabricated by wet etch technology,” Microelectronics J. 36(7), 650–656 (2005).
[Crossref]

Windmiller, J. R.

G. Valdés-Ramírez, J. R. Windmiller, J. C. Claussen, A. G. Martinez, F. Kuralay, M. Zhou, N. Zhou, R. Polsky, P. R. Miller, R. Narayan, and J. Wang, “Multiplexed and switchable release of distinct fluids from microneedle platforms via conducting polymer nanoactuators for potential drug delivery,” Sens. Actuators B Chem. 161(1), 1018–1024 (2012).
[Crossref] [PubMed]

Woolfson, A. D.

E. Larrañeta, J. Moore, E. M. Vicente-Pérez, P. González-Vázquez, R. Lutton, A. D. Woolfson, and R. F. Donnelly, “A proposed model membrane and test method for microneedle insertion studies,” Int. J. Pharm. 472(1-2), 65–73 (2014).
[Crossref] [PubMed]

R. F. Donnelly, T. R. R. Singh, M. J. Garland, K. Migalska, R. Majithiya, C. M. McCrudden, P. L. Kole, T. M. T. Mahmood, H. O. McCarthy, and A. D. Woolfson, “Hydrogel-forming microneedle arrays for enhanced transdermal drug delivery,” Adv. Funct. Mater. 22(23), 4879–4890 (2012).
[Crossref] [PubMed]

R. F. Donnelly, T. R. Raj Singh, and A. D. Woolfson, “Microneedle-based drug delivery systems: Microfabrication, drug delivery, and safety,” Drug Deliv. 17(4), 187–207 (2010).
[Crossref] [PubMed]

Xiao, X.

P. R. Miller, S. A. Skoog, T. L. Edwards, D. M. Lopez, D. R. Wheeler, D. C. Arango, X. Xiao, S. M. Brozik, J. Wang, R. Polsky, and R. J. Narayan, “Multiplexed Microneedle-based Biosensor Array for Characterization of Metabolic Acidosis,” Talanta 88, 739–742 (2012).
[Crossref] [PubMed]

Ye, S.-R.

N. Wilke, A. Mulcahy, S.-R. Ye, and A. Morrissey, “Process optimization and characterization of silicon microneedles fabricated by wet etch technology,” Microelectronics J. 36(7), 650–656 (2005).
[Crossref]

Yu, Y.

H. Li, Y. Yu, S. Faraji Dana, B. Li, C.-Y. Lee, and L. Kang, “Novel engineered systems for oral, mucosal and transdermal drug delivery,” J. Drug Target. 21(7), 611–629 (2013).
[Crossref] [PubMed]

Zhou, M.

G. Valdés-Ramírez, J. R. Windmiller, J. C. Claussen, A. G. Martinez, F. Kuralay, M. Zhou, N. Zhou, R. Polsky, P. R. Miller, R. Narayan, and J. Wang, “Multiplexed and switchable release of distinct fluids from microneedle platforms via conducting polymer nanoactuators for potential drug delivery,” Sens. Actuators B Chem. 161(1), 1018–1024 (2012).
[Crossref] [PubMed]

Zhou, N.

G. Valdés-Ramírez, J. R. Windmiller, J. C. Claussen, A. G. Martinez, F. Kuralay, M. Zhou, N. Zhou, R. Polsky, P. R. Miller, R. Narayan, and J. Wang, “Multiplexed and switchable release of distinct fluids from microneedle platforms via conducting polymer nanoactuators for potential drug delivery,” Sens. Actuators B Chem. 161(1), 1018–1024 (2012).
[Crossref] [PubMed]

Zou, S.

J. S. Kochhar, W. X. S. Lim, S. Zou, W. Y. Foo, J. Pan, and L. Kang, “Microneedle Integrated Transdermal Patch for Fast Onset and Sustained Delivery of Lidocaine,” Mol. Pharm. 10(11), 4272–4280 (2013).
[Crossref] [PubMed]

Acta Biomater. (1)

J. R. Henstock, L. T. Canham, and S. I. Anderson, “Silicon: The evolution of its use in biomaterials,” Acta Biomater. 11, 17–26 (2015).
[Crossref] [PubMed]

Adv. Funct. Mater. (2)

R. Vecchione, S. Coppola, E. Esposito, C. Casale, V. Vespini, S. Grilli, P. Ferraro, and P. A. Netti, “Electro-Drawn Drug-Loaded Biodegradable Polymer Microneedles as a Viable Route to Hypodermic Injection,” Adv. Funct. Mater. 24(23), 3515–3523 (2014).
[Crossref]

R. F. Donnelly, T. R. R. Singh, M. J. Garland, K. Migalska, R. Majithiya, C. M. McCrudden, P. L. Kole, T. M. T. Mahmood, H. O. McCarthy, and A. D. Woolfson, “Hydrogel-forming microneedle arrays for enhanced transdermal drug delivery,” Adv. Funct. Mater. 22(23), 4879–4890 (2012).
[Crossref] [PubMed]

Adv. Healthc. Mater. (1)

L. Ventrelli, L. Marsilio Strambini, and G. Barillaro, “Microneedles for Transdermal Biosensing: Current Picture and Future Direction,” Adv. Healthc. Mater. 4(17), 2606–2640 (2015).
[Crossref] [PubMed]

Adv. Mater. (1)

L. De Stefano, I. Rea, P. Giardina, A. Armenante, and I. Rendina, “Protein modified porous silicon nanostructures,” Adv. Mater. 20(8), 1529–1533 (2008).
[Crossref]

Anesth. Analg. (1)

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(2), 502–504 (2001).
[Crossref] [PubMed]

Bioconjug. Chem. (1)

E. M. Cahill and E. D. O’Cearbhaill, “Toward Biofunctional Microneedles for Stimulus Responsive Drug Delivery,” Bioconjug. Chem. 26(7), 1289–1296 (2015).
[Crossref] [PubMed]

Biomaterials (1)

M. B. Mellott, K. Searcy, and M. V. Pishko, “Release of protein from highly cross-linked hydrogels of poly(ethylene glycol) diacrylate fabricated by UV polymerization,” Biomaterials 22(9), 929–941 (2001).
[Crossref] [PubMed]

Br. J. Dermatol. (1)

F. Chabri, K. Bouris, T. Jones, D. Barrow, A. Hann, C. Allender, K. Brain, and J. Birchall, “Microfabricated silicon microneedles for nonviral cutaneous gene delivery,” Br. J. Dermatol. 150(5), 869–877 (2004).
[Crossref] [PubMed]

Crit. Rev. Ther. Drug Carrier Syst. (1)

M. R. Prausnitz, “Reversible skin permeabilization for transdermal delivery of macromolecules,” Crit. Rev. Ther. Drug Carrier Syst. 14(4), 455–483 (1997).
[Crossref] [PubMed]

Drug Deliv. (1)

R. F. Donnelly, T. R. Raj Singh, and A. D. Woolfson, “Microneedle-based drug delivery systems: Microfabrication, drug delivery, and safety,” Drug Deliv. 17(4), 187–207 (2010).
[Crossref] [PubMed]

Int. J. Mol. Sci. (1)

M. W. Ashraf, S. Tayyaba, and N. Afzulpurkar, “Micro Electromechanical Systems (MEMS) Based Microfluidic Devices for Biomedical Applications,” Int. J. Mol. Sci. 12(6), 3648–3704 (2011).
[Crossref] [PubMed]

Int. J. Pharm. (1)

E. Larrañeta, J. Moore, E. M. Vicente-Pérez, P. González-Vázquez, R. Lutton, A. D. Woolfson, and R. F. Donnelly, “A proposed model membrane and test method for microneedle insertion studies,” Int. J. Pharm. 472(1-2), 65–73 (2014).
[Crossref] [PubMed]

J. Drug Target. (1)

H. Li, Y. Yu, S. Faraji Dana, B. Li, C.-Y. Lee, and L. Kang, “Novel engineered systems for oral, mucosal and transdermal drug delivery,” J. Drug Target. 21(7), 611–629 (2013).
[Crossref] [PubMed]

J. Pharm. Sci. (1)

S. Henry, D. V. McAllister, M. G. Allen, and M. R. Prausnitz, “Microfabricated Microneedles: A Novel Approach to Transdermal Drug Delivery,” J. Pharm. Sci. 87(8), 922–925 (1998).
[Crossref] [PubMed]

J. Proteome Res. (1)

L. De Stefano, M. Rossi, M. Staiano, G. Mamone, A. Parracino, L. Rotiroti, I. Rendina, M. Rossi, and S. D’Auria, “Glutamine-binding protein from Escherichia coli specifically binds a wheat gliadin peptide allowing the design of a new porous silicon-based optical biosensor,” J. Proteome Res. 5(5), 1241–1245 (2006).
[Crossref] [PubMed]

Materials (Basel) (1)

P. Dardano, A. Caliò, V. Di Palma, M. F. Bevilacqua, A. Di Matteo, and L. De Stefano, “Photolithographic approaches to polymeric microneedles array fabrication for biomedical applications,” Materials (Basel) 8(12), 8661–8673 (2015).
[Crossref]

Microelectronics J. (1)

N. Wilke, A. Mulcahy, S.-R. Ye, and A. Morrissey, “Process optimization and characterization of silicon microneedles fabricated by wet etch technology,” Microelectronics J. 36(7), 650–656 (2005).
[Crossref]

Mol. Pharm. (1)

J. S. Kochhar, W. X. S. Lim, S. Zou, W. Y. Foo, J. Pan, and L. Kang, “Microneedle Integrated Transdermal Patch for Fast Onset and Sustained Delivery of Lidocaine,” Mol. Pharm. 10(11), 4272–4280 (2013).
[Crossref] [PubMed]

Nat. Biotechnol. (1)

M. R. Prausnitz and R. Langer, “Transdermal drug delivery,” Nat. Biotechnol. 26(11), 1261–1268 (2008).
[Crossref] [PubMed]

Physica E (1)

I. Rendina, I. Rea, L. Rotiroti, and L. De Stefano, “Porous Silicon Based Optical Biosensors and Biochips,” Physica E 38(1-2), 188–192 (2007).
[Crossref]

Proc. Natl. Acad. Sci. U.S.A. (1)

J. L. Tan, J. Tien, D. M. Pirone, D. S. Gray, K. Bhadriraju, and C. S. Chen, “Cells lying on a bed of microneedles: An approach to isolate mechanical force,” Proc. Natl. Acad. Sci. U.S.A. 100(4), 1484–1489 (2003).
[Crossref] [PubMed]

Sens. Actuators A Phys. (1)

E. V. Mukerjee, S. D. Collins, R. R. Isseroff, and R. L. Smith, “Microneedle array for transdermal biological fluid extraction and in situ analysis,” Sens. Actuators A Phys. 114(2-3), 267–275 (2004).
[Crossref]

Sens. Actuators B Chem. (2)

G. Valdés-Ramírez, J. R. Windmiller, J. C. Claussen, A. G. Martinez, F. Kuralay, M. Zhou, N. Zhou, R. Polsky, P. R. Miller, R. Narayan, and J. Wang, “Multiplexed and switchable release of distinct fluids from microneedle platforms via conducting polymer nanoactuators for potential drug delivery,” Sens. Actuators B Chem. 161(1), 1018–1024 (2012).
[Crossref] [PubMed]

L. De Stefano, L. Moretti, I. Rendina, and A. M. Rossi, “Time-resolved sensing of chemical species in porous silicon optical microcavity,” Sens. Actuators B Chem. 100(1-2), 168–172 (2004).
[Crossref]

Talanta (1)

P. R. Miller, S. A. Skoog, T. L. Edwards, D. M. Lopez, D. R. Wheeler, D. C. Arango, X. Xiao, S. M. Brozik, J. Wang, R. Polsky, and R. J. Narayan, “Multiplexed Microneedle-based Biosensor Array for Characterization of Metabolic Acidosis,” Talanta 88, 739–742 (2012).
[Crossref] [PubMed]

Other (1)

Prof. L. T. Canham, pSiMedica Ltd, Malvern Hills Science Park, Malvern, Worcerstershire, WR14 35Z, UK, private communication.

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Figures (9)

Fig. 1
Fig. 1 Microneedles array process flow: photolithographic standard approach allows low cost fabrication of large area MNs array. Steps 1-6 are recalled in text in Fabrication process paragraph.
Fig. 2
Fig. 2 Schematic of hybrid patch assembling: the porous silicon oxidized free-standing membrane is placed on PEGDA support (a); then the active molecules are loaded in its spongy matrix (b) and the MNs array is bonded by UV exposure (c and d). In the inset, microphotograph by electron scanning microscopy of PSi real sample and a digital image of the assembled patch are reported.
Fig. 3
Fig. 3 MNs array characterization: (a) MNs array flexibility; (b) micro-images of a single needle; (c) macroscopic view of MNs; (d) tip measurement. The MNs array on PEGDA has good flexibility useful for patch applications. The MNs have highness, shapes and curvature radii tunable by changing process parameters.
Fig. 4
Fig. 4 Sketch of device operation: the PSiM is loaded with fluorescein molecules (a), fluorescein diffuses into the MNs nanoporous (b) and it is released into the PBS solution as effect of the MNs swelling(c).
Fig. 5
Fig. 5 (a) Top view of the device acquired in bright field mode: the blue line underlines the profile of the porous silicon membrane placed under the microneedles (right side) with respect to the only microneedles (left side); (b) Top view of the device acquired in fluorescence mode with the same field of view of (a): the image shows that only the area overlapping the porous silicon membrane is fluorescent (right side). (c) Fluorescence intensity of areas inside the red rectangles calculated using ImageJ software; (d) Lateral view of the device acquired in fluorescence mode: the blue line underlines the profile of the porous silicon membrane placed under the microneedles. (e) A single microneedle detached from the device after fluorescein loading shows that the fluorescein is almost uniformly distributed from the base to the tip.
Fig. 6
Fig. 6 Spectroscopic reflectometry (a) and naked eye (b) characterizations after oxidation, fluorescein loading and release.
Fig. 7
Fig. 7 Calibration curve of fluorescein loading into Bragg mirror optical structure b); correspondent optical spectra a).
Fig. 8
Fig. 8 Fluorescence intensity of the device changes as function of time of fluorescein release in PBS. The control shows that intensity fluorescence decreasing is not due to fluorescence decay.
Fig. 9
Fig. 9 Comparison between the estimated fluorescein released in PBS and data of in vitro release as reported in ref [16].

Tables (1)

Tables Icon

Table 1 Spectroscopic reflectometry data of absolute position and shift of Bragg optical structure peak as function of immersion time in phosphate buffer saline.

Metrics