Abstract

We achieved continuous, noncontact wide-field imaging and characterization of drug release from a polymeric device in vitro by uniquely using off-axis interferometric imaging. Unlike the current gold-standard methods in this field, which are usually based on chromatography and spectroscopy, our method requires no user intervention during the experiment and involves less lab consumable instruments. Using a simplified interferometric imaging system, we experimentally demonstrate the characterization of anesthetic drug release (Bupivacaine) from a soy-based protein matrix, which is used as a skin substitute for wound dressing. Our results demonstrate the potential of interferometric imaging as an inexpensive and easy-to-use alternative for characterization of drug release in vitro.

© 2013 Optical Society of America

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References

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  1. J. Heller, Biomaterials 1, 51 (1980).
    [CrossRef]
  2. L. G. Griffith, Acta Mater. 48, 263 (2000).
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    [CrossRef]
  4. A. Bhatnagar, R. Hustinx, and A. Alavi, Adv. Drug Delivery Rev. 41, 41 (2000).
    [CrossRef]
  5. J. S. Taylor and W. E. Reddick, Adv. Drug Delivery Rev. 41, 91 (2000).
    [CrossRef]
  6. L. R. Snyder, J. J. Kirkland, and J. W. Dolan, Introduction to Modern Liquid Chromatography (Wiley, 2011).
  7. H. Gabai and N. T. Shaked, Opt. Express 20, 26906 (2012).
    [CrossRef]
  8. J. A. Ferrari and E. M. Frins, Opt. Commun. 279, 235 (2007).
    [CrossRef]
  9. Z. Peles and M. Zilberman, Acta Biomat. 8, 209 (2012).
    [CrossRef]
  10. M. Baranes-Zeevi and M. Zilberman, “Formulation-property effects in soy-protein based structure with drug delivery for wound healing applications,” J. Biomed. Mater. Res., submitted for publication.
  11. J. Mertz, in Introduction to Optical Microscopy (Roberts and Company Publishers, 2010), pp. 13–26.
  12. L. Rodgers, J. Nicewander, and W. A. Nicewander, Am. Stat. 42, 59 (1988).
    [CrossRef]
  13. S. Dash, P. N. Murthy, L. Nath, and P. Chowdhury, Acta Poloniae Pharmaceutica 67, 217 (2010).
  14. K. Kosmidis, P. Argyrakis, and P. Macheras, Pharm. Res. 20, 988 (2003).
    [CrossRef]
  15. V. Papadopoulou, K. Kosmidis, M. Vlachou, and P. Macheras, Int. J. Pharm. 309, 44 (2006).
    [CrossRef]

2012

H. Gabai and N. T. Shaked, Opt. Express 20, 26906 (2012).
[CrossRef]

Z. Peles and M. Zilberman, Acta Biomat. 8, 209 (2012).
[CrossRef]

2010

S. Dash, P. N. Murthy, L. Nath, and P. Chowdhury, Acta Poloniae Pharmaceutica 67, 217 (2010).

2007

J. A. Ferrari and E. M. Frins, Opt. Commun. 279, 235 (2007).
[CrossRef]

2006

V. Papadopoulou, K. Kosmidis, M. Vlachou, and P. Macheras, Int. J. Pharm. 309, 44 (2006).
[CrossRef]

2003

K. Kosmidis, P. Argyrakis, and P. Macheras, Pharm. Res. 20, 988 (2003).
[CrossRef]

A. Szymanski-Exner, N. T. Stowe, K. Salem, R. Lazebnik, J. R. Haaga, D. L. Wilson, and J. Gao, J. Pharm. Sci. 92, 289 (2003).
[CrossRef]

2000

A. Bhatnagar, R. Hustinx, and A. Alavi, Adv. Drug Delivery Rev. 41, 41 (2000).
[CrossRef]

J. S. Taylor and W. E. Reddick, Adv. Drug Delivery Rev. 41, 91 (2000).
[CrossRef]

L. G. Griffith, Acta Mater. 48, 263 (2000).
[CrossRef]

1988

L. Rodgers, J. Nicewander, and W. A. Nicewander, Am. Stat. 42, 59 (1988).
[CrossRef]

1980

J. Heller, Biomaterials 1, 51 (1980).
[CrossRef]

Alavi, A.

A. Bhatnagar, R. Hustinx, and A. Alavi, Adv. Drug Delivery Rev. 41, 41 (2000).
[CrossRef]

Argyrakis, P.

K. Kosmidis, P. Argyrakis, and P. Macheras, Pharm. Res. 20, 988 (2003).
[CrossRef]

Baranes-Zeevi, M.

M. Baranes-Zeevi and M. Zilberman, “Formulation-property effects in soy-protein based structure with drug delivery for wound healing applications,” J. Biomed. Mater. Res., submitted for publication.

Bhatnagar, A.

A. Bhatnagar, R. Hustinx, and A. Alavi, Adv. Drug Delivery Rev. 41, 41 (2000).
[CrossRef]

Chowdhury, P.

S. Dash, P. N. Murthy, L. Nath, and P. Chowdhury, Acta Poloniae Pharmaceutica 67, 217 (2010).

Dash, S.

S. Dash, P. N. Murthy, L. Nath, and P. Chowdhury, Acta Poloniae Pharmaceutica 67, 217 (2010).

Dolan, J. W.

L. R. Snyder, J. J. Kirkland, and J. W. Dolan, Introduction to Modern Liquid Chromatography (Wiley, 2011).

Ferrari, J. A.

J. A. Ferrari and E. M. Frins, Opt. Commun. 279, 235 (2007).
[CrossRef]

Frins, E. M.

J. A. Ferrari and E. M. Frins, Opt. Commun. 279, 235 (2007).
[CrossRef]

Gabai, H.

Gao, J.

A. Szymanski-Exner, N. T. Stowe, K. Salem, R. Lazebnik, J. R. Haaga, D. L. Wilson, and J. Gao, J. Pharm. Sci. 92, 289 (2003).
[CrossRef]

Griffith, L. G.

L. G. Griffith, Acta Mater. 48, 263 (2000).
[CrossRef]

Haaga, J. R.

A. Szymanski-Exner, N. T. Stowe, K. Salem, R. Lazebnik, J. R. Haaga, D. L. Wilson, and J. Gao, J. Pharm. Sci. 92, 289 (2003).
[CrossRef]

Heller, J.

J. Heller, Biomaterials 1, 51 (1980).
[CrossRef]

Hustinx, R.

A. Bhatnagar, R. Hustinx, and A. Alavi, Adv. Drug Delivery Rev. 41, 41 (2000).
[CrossRef]

Kirkland, J. J.

L. R. Snyder, J. J. Kirkland, and J. W. Dolan, Introduction to Modern Liquid Chromatography (Wiley, 2011).

Kosmidis, K.

V. Papadopoulou, K. Kosmidis, M. Vlachou, and P. Macheras, Int. J. Pharm. 309, 44 (2006).
[CrossRef]

K. Kosmidis, P. Argyrakis, and P. Macheras, Pharm. Res. 20, 988 (2003).
[CrossRef]

Lazebnik, R.

A. Szymanski-Exner, N. T. Stowe, K. Salem, R. Lazebnik, J. R. Haaga, D. L. Wilson, and J. Gao, J. Pharm. Sci. 92, 289 (2003).
[CrossRef]

Macheras, P.

V. Papadopoulou, K. Kosmidis, M. Vlachou, and P. Macheras, Int. J. Pharm. 309, 44 (2006).
[CrossRef]

K. Kosmidis, P. Argyrakis, and P. Macheras, Pharm. Res. 20, 988 (2003).
[CrossRef]

Mertz, J.

J. Mertz, in Introduction to Optical Microscopy (Roberts and Company Publishers, 2010), pp. 13–26.

Murthy, P. N.

S. Dash, P. N. Murthy, L. Nath, and P. Chowdhury, Acta Poloniae Pharmaceutica 67, 217 (2010).

Nath, L.

S. Dash, P. N. Murthy, L. Nath, and P. Chowdhury, Acta Poloniae Pharmaceutica 67, 217 (2010).

Nicewander, J.

L. Rodgers, J. Nicewander, and W. A. Nicewander, Am. Stat. 42, 59 (1988).
[CrossRef]

Nicewander, W. A.

L. Rodgers, J. Nicewander, and W. A. Nicewander, Am. Stat. 42, 59 (1988).
[CrossRef]

Papadopoulou, V.

V. Papadopoulou, K. Kosmidis, M. Vlachou, and P. Macheras, Int. J. Pharm. 309, 44 (2006).
[CrossRef]

Peles, Z.

Z. Peles and M. Zilberman, Acta Biomat. 8, 209 (2012).
[CrossRef]

Reddick, W. E.

J. S. Taylor and W. E. Reddick, Adv. Drug Delivery Rev. 41, 91 (2000).
[CrossRef]

Rodgers, L.

L. Rodgers, J. Nicewander, and W. A. Nicewander, Am. Stat. 42, 59 (1988).
[CrossRef]

Salem, K.

A. Szymanski-Exner, N. T. Stowe, K. Salem, R. Lazebnik, J. R. Haaga, D. L. Wilson, and J. Gao, J. Pharm. Sci. 92, 289 (2003).
[CrossRef]

Shaked, N. T.

Snyder, L. R.

L. R. Snyder, J. J. Kirkland, and J. W. Dolan, Introduction to Modern Liquid Chromatography (Wiley, 2011).

Stowe, N. T.

A. Szymanski-Exner, N. T. Stowe, K. Salem, R. Lazebnik, J. R. Haaga, D. L. Wilson, and J. Gao, J. Pharm. Sci. 92, 289 (2003).
[CrossRef]

Szymanski-Exner, A.

A. Szymanski-Exner, N. T. Stowe, K. Salem, R. Lazebnik, J. R. Haaga, D. L. Wilson, and J. Gao, J. Pharm. Sci. 92, 289 (2003).
[CrossRef]

Taylor, J. S.

J. S. Taylor and W. E. Reddick, Adv. Drug Delivery Rev. 41, 91 (2000).
[CrossRef]

Vlachou, M.

V. Papadopoulou, K. Kosmidis, M. Vlachou, and P. Macheras, Int. J. Pharm. 309, 44 (2006).
[CrossRef]

Wilson, D. L.

A. Szymanski-Exner, N. T. Stowe, K. Salem, R. Lazebnik, J. R. Haaga, D. L. Wilson, and J. Gao, J. Pharm. Sci. 92, 289 (2003).
[CrossRef]

Zilberman, M.

Z. Peles and M. Zilberman, Acta Biomat. 8, 209 (2012).
[CrossRef]

M. Baranes-Zeevi and M. Zilberman, “Formulation-property effects in soy-protein based structure with drug delivery for wound healing applications,” J. Biomed. Mater. Res., submitted for publication.

Acta Biomat.

Z. Peles and M. Zilberman, Acta Biomat. 8, 209 (2012).
[CrossRef]

Acta Mater.

L. G. Griffith, Acta Mater. 48, 263 (2000).
[CrossRef]

Acta Poloniae Pharmaceutica

S. Dash, P. N. Murthy, L. Nath, and P. Chowdhury, Acta Poloniae Pharmaceutica 67, 217 (2010).

Adv. Drug Delivery Rev.

A. Bhatnagar, R. Hustinx, and A. Alavi, Adv. Drug Delivery Rev. 41, 41 (2000).
[CrossRef]

J. S. Taylor and W. E. Reddick, Adv. Drug Delivery Rev. 41, 91 (2000).
[CrossRef]

Am. Stat.

L. Rodgers, J. Nicewander, and W. A. Nicewander, Am. Stat. 42, 59 (1988).
[CrossRef]

Biomaterials

J. Heller, Biomaterials 1, 51 (1980).
[CrossRef]

Int. J. Pharm.

V. Papadopoulou, K. Kosmidis, M. Vlachou, and P. Macheras, Int. J. Pharm. 309, 44 (2006).
[CrossRef]

J. Pharm. Sci.

A. Szymanski-Exner, N. T. Stowe, K. Salem, R. Lazebnik, J. R. Haaga, D. L. Wilson, and J. Gao, J. Pharm. Sci. 92, 289 (2003).
[CrossRef]

Opt. Commun.

J. A. Ferrari and E. M. Frins, Opt. Commun. 279, 235 (2007).
[CrossRef]

Opt. Express

Pharm. Res.

K. Kosmidis, P. Argyrakis, and P. Macheras, Pharm. Res. 20, 988 (2003).
[CrossRef]

Other

M. Baranes-Zeevi and M. Zilberman, “Formulation-property effects in soy-protein based structure with drug delivery for wound healing applications,” J. Biomed. Mater. Res., submitted for publication.

J. Mertz, in Introduction to Optical Microscopy (Roberts and Company Publishers, 2010), pp. 13–26.

L. R. Snyder, J. J. Kirkland, and J. W. Dolan, Introduction to Modern Liquid Chromatography (Wiley, 2011).

Supplementary Material (1)

» Media 1: AVI (2914 KB)     

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Figures (4)

Fig. 1.
Fig. 1.

Experimental setup. HeNe: Helium–Neon laser; L0-5: lenses (f=35, 50, 45, 150, 75, 40 mm); P: 25 μm pinhole; M: mirror. The coverslip is covered by a chamber-like silicon sticker, divided by a thin silicon bar into two sections coinciding with the reference arm R and sample arm S. DDD: drug delivery device (located outside the FOV); BS: beam splitter; blue lines: reference arm; green lines: sample arm; solid lines in the BS: transmitted light; dashed lines in the BS: reflected light; CMOS: conventional CMOS camera (DCC1545M, Thorlabs, 1280×1024 square pixels of 5.2 μm2).

Fig. 2.
Fig. 2.

Cumulative drug-release profiles obtained from HPLC (solid line), off-axis interferometry (dotted line), and Weibull model (crossed line) for drug release period of 12 h.

Fig. 3.
Fig. 3.

Quantitative phase profile resulted from drug release during 12 h, as measured by continuous wide-field interferometric imaging. The right lower frame illustrates the DDD location relatively to the FOV. See full dynamics in Media 1.

Fig. 4.
Fig. 4.

Normalized dynamic phase profile, used as local drug-release estimator, for 34 locations, starting from the most proximate location to the DDD (marked as P1) to the most distant location from the DDD (marked as P2).

Tables (1)

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Table 1. Comparison between the Different Approaches

Equations (3)

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OPD(x,y)=0htot[ntot(x,y,z)nm]dz=hd(x,y)nd+[htothd(x,y)]nmhtotnm=hd(x,y)[ndnm]
α=1N·i=1NC(i)φ¯(i),
C(t)=Cend·[1exp(ttd)β],

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